BACKGROUND OF THE INVENTION Currently, there is a general belief that all organs contain stem cells, but that the technology to recognise them either by location or characteristic morphology and surface molecule expression (Al-Awqati & Oliver, 2002, Kidney Int. 61 387-395) has not been developed. Although cell division is infrequent in the adult kidney, this organ possesses the capacity for regeneration, as witnessed by the cellular proliferation during recovery from conditions such as acute tubular necrosis (Shankland et al., 2000, Am. J. Physiol. 278 F515-F529). However, it is unknown whether this represents the persistence of renal progenitors or their origin.

The developed kidney arises via reciprocal interactions between two tissues, the ureteric bud (UB) and the metanephric mesenchyme (MM). Each of these tissues is initially derived from the intermediate mesoderm (IM). The central dogma of kidney development implies that the UB forms the ureter and collecting duct system of the mature kidney while the MM gives rise to the remaining portions of the nephrons, from Bowmans's capsule to distal tubule.

The undifferentiated MM can therefore be regarded as the renal progenitor population, a homogenous mass of cells with multipotent differentiation capacity, because it has the ability to differentiate into many more differentiated cell types than do the UB precursors (Herzlinger et al., 1992, Development 114 565-572).

This suggests that of the two primordial tissues that interact to produce a mature

kidney, the MM is more likely to be the source of a renal stem cell population rather than the UB. However, both entities are initially derived from IM tissue and the UB may be regarded as providing more specific progenitors for the collecting system of the kidney only.

Several reports have generated evidence that supports the notion of the undifferentiated MM acting as or containing a mesodermal stem cell population.

Lineage-tracing studies have suggested that the uncommitted MM not only has the potential to develop into all the epithelial regions of the nephron, but also can be incorporated into collecting duct epithelia (Qiao et al., 1995, Development 121 3207-3214). Further evidence for the developmental potential of this tissue was recognised when embryonic porcine metanephroi transplanted into immunodeficient mice developed non-renal derivatives such as cartilage and bone in addition to mature glomeruli and tubuli (Dekel et al., 2003, Nat. Med. 9 53-60).

Several other studies of cell lines isolated from early, uninduced metanephric mesenchyme have indicated that the MM displays multipotentiality (Herzlinger et al., 1991, J. Am. Soc. Nephrol. 2 438; Oliver et al., 2002, Am. , J. Physiol. 283 F799-F809; Herzlinger et al., 1992, supra). In vivo experiments have yet to confirm these findings.

While many of the interactions between the UB and MM are now well characterised, the processes by which the MM differentiates from surrounding intermediate mesoderm (IM) and becomes committed to a renal fate remain poorly understood. The creation of the MM depends on the temporary embryonic kidneys, the pronephroi and mesonephroi, developing normally first (Davies & Fisher, 2002, Exp. Neph. 10 102-113). Gene-targeting studies have suggested that expression of the transcription factors Liml (Fujii et al., 1994, Dev. Dyn. 199 211-230), Pax2 (Torres et al., 1995, Development 121 4057-4065), Eyal (Xu et al., 1999, Nat. Gen. 23 113-117) and WT1 (Kreidberg et al., 1993, Cell 74 679- 691) are some of the earliest signs of commitment of the MM to a renal fate, even though the precise role of these genes in kidney development is not fully understood and their expression is not restricted to the MM but extend also to the adjacent mesonephros and gonad as well as to more distant sites, including eye and neural tissue. Microarrays have been used to generate temporal profiles of

gene expression over the course of metanephric development (Stuart et al., 2001, Proc. Natl. Acad. Sci. USA 98 5649-5654; Schwab et al., 2003, Kidney Int. 64 1588-1604) and to analyse the expression profiles of discrete renal subcompartments (Stuart et al., Kidney Int. 64 1997-2008). Nevertheless, gene expression by the MM at the earlier renal progenitor stage is unknown.

SUMMARY OF THE INVENTION The present invention broadly relates to defining a gene expression profile that facilitates identification, isolation and/or purification of committed but undifferentiated metanephric mesenchyme cells, including renal progenitor cells.

In a first aspect, the invention provides a method of identifying a gene expression profile associated with metanephric mesenchyme development, said method including the step of identifying one or more genes that are differentially expressed by one or more metanephric mesenchyme cells at a particular stage of embryonic development compared to one or more intermediate mesoderm cells.

In a second aspect, the invention provides a method of identifying a metanephric mesenchyme cell, said method including the step of determining a gene expression profile of said metanephric mesenchyme cell, wherein said gene expression profile comprises one or more genetic markers that are differentially expressed by one or more metanephric mesenchyme cells compared to one or more intermediate mesoderm cells.

In a third aspect, the invention provides a method of isolating or purifying one or more metanephric mesenchyme cells including the step of identifying a gene expression profile that comprises one or more genetic markers that are differentially expressed by said one or more metanephric mesenchyme cells compared to one or more intermediate mesoderm cells. There has to be something said in this aspect and in the fifth aspect about the markers needing to be at the cell surface for the purposes of isolation.

In one embodiment, gene expression is determined according to nucleic acid expression, such as mRNA expression.

In another embodiment, gene expression is determined according to protein expression.

In preferred embodiments, expressed genes that may be used in gene expression profiles associated with a particular stage of development of metanephric mesenchyme, which genes are differentially expressed with respect to IM, are set forth in Tables 2 and 3.

In a particularly preferred form, the gene expression profile comprises one or more genetic markers set forth in Table 4.

In embodiments relating to isolation and purification of metanephric mesenchyme cells, advantageous cell surface markers include Neuropilin-1 ; CD164 antigen; CD83 antigen; Stromal cell derived factor receptor 1; CD24a antigen; Serine protease inhibitor, Kunitz type 2; Tumor-associated calcium signal transducer 1 ; Receptor-like tyrosine kinase; Fibroblast growth factor receptor 2; Amyloid beta (A4) precursor protein; Bone morphogenetic protein receptor, type 1A ; DNA segment, Chr 8, Wayne State University 49, expressed; Signal sequence receptor, alpha; Junction adhesion molecule 3; PTK7 protein tyrosine kinase 7; Cadherin 11; Syndecan binding protein; Integral membrane protein 2C; Tripartite motif-containing 59; NAD (P) dependent steroid dehydrogenase-like; DNA segment, Chr 3, University of California at Los Angeles 1; Solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2; RIKEN cDNA 1110018G07 gene; Purine rich element binding protein B; Solute carrier family 6 (neurotransmitter transporter, taurine), member 6; Gap junction membrane channel protein alpha 1 ; Tumor differentially expressed 1 ; CD81 antigen; Solute carrier family 35, member 5; Solute carrier family 39 (zinc transporter), member 7; Gene rich cluster, C3f gene; Claudin 6; Solute carrier family 20, member 1; Solute carrier family 16 (monocarboxylic acid transporters), member 1; ADP-ribosylation factor-like 6 interacting protein 2; Autocrine motility factor receptor; Claudin 7; Calcitonin receptor-like; Tumor differentially expressed 2; Synaptophysin-like protein; Claudin 11; G protein- coupled receptor 89 ; ELOVL family member 6 (Elovl6), elongation of long chain fatty acids (yeast); Purinergic receptor (family A group 5); Non imprinted in Prader-Willi/Angelman syndrome 2 homolog (human); RIKEN cDNA 4930579A11 gene; Zinc finger, DHHC domain containing 6; Solute carrier family 37 (glycerol-3-phosphate transporter), member 3; Sarcoma amplified

sequence; RIKEN cDNA 1700022N24 gene; and Mid-1-related chloride channel 1, although without limitation thereto, either singly or in combination.

In a fourth aspect, the invention provides a method of identifying a gene expression profile of a renal progenitor cell, said method including the step of identifying one or more genes that are differentially expressed by said renal progenitor cell compared to an intermediate mesenchyme cell.

In a fifth aspect, the invention provides a method of identifying a renal progenitor cell, said method including the step of determining a gene expression profile of said renal progenitor cell, wherein the gene expression profile comprises one or more genetic markers differentially expressed compared to an intermediate mesenchyme cell.

In a sixth aspect, the invention provides a method of isolating or purifying a renal progenitor cell, said method including the step of identifying a gene expression profile of said renal progenitor cell, wherein the gene expression profile comprises one or more genetic markers differentially expressed compared to an intermediate mesenchyme cell.

Typically, said renal progenitor cell is isolated from differentiating embryonic or adult stem cells in culture or from any adult tissue, including the kidney.

In preferred embodiments, expressed genes that may be used in gene expression profiles associated with renal progenitor cells are set forth in Tables 2 and 3.

In a particularly preferred form, the gene expression profile comprises one or more genetic markers set forth in Table 4.

In embodiments relating to isolation and purification of renal progenitor cells, advantageous cell surface markers include Neuropilin-1 ; CD164 antigen; CD83 antigen; Stromal cell derived factor receptor 1; CD24a antigen; Serine protease inhibitor, Kunitz type 2; Tumor-associated calcium signal transducer 1; Receptor-like tyrosine kinase; Fibroblast growth factor receptor 2; Amyloid beta (A4) precursor protein; Bone morphogenetic protein receptor, type 1A ; DNA segment, Chr 8, Wayne State University 49, expressed; Signal sequence receptor, alpha; Junction adhesion molecule 3; PTK7 protein tyrosine kinase 7; Cadherin

11; Syndecan binding protein; Integral membrane protein 2C ; Tripartite motif- containing 59; NAD (P) dependent steroid dehydrogenase-like; DNA segment, Chr 3, University of California at Los Angeles 1; Solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2; RIKEN cDNA 1110018G07 gene; Purine rich element binding protein B; Solute carrier family 6 (neurotransmitter transporter, taurine), member 6; Gap junction membrane channel protein alpha 1; Tumor differentially expressed 1; CD81 antigen; Solute carrier family 35, member 5; Solute carrier family 39 (zinc transporter), member 7; Gene rich cluster, C3f gene; Claudin 6; Solute carrier family 20, member 1; Solute carrier family 16 (monocarboxylic acid transporters), member 1; ADP- ribosylation factor-like 6 interacting protein 2; Autocrine motility factor receptor; Claudin 7; Calcitonin receptor-like; Tumor differentially expressed 2; Synaptophysin-like protein; Claudin 11; G protein-coupled receptor 89 ; ELOVL family member 6 (Elovl6), elongation of long chain fatty acids (yeast); Purinergic receptor (family A group 5); Non imprinted in Prader-Willi/Angelman syndrome 2 homolog (human) ; RIKEN cDNA 4930579All gene; Zinc finger, DHHC domain containing 6; Solute carrier family 37 (glycerol-3-phosphate transporter), member 3; Sarcoma amplified sequence; RIKEN cDNA 1700022N24 gene; and Mid-l-related chloride channel 1, although without limitation thereto, either singly or in combination.

The cell surface markers profile may further comprise one or more cell surface markers together with one or more other stem cell markers as described in Table 6.

Preferably, the one or more other stem cell markers are selected from the group consisting of CD34, c-kit and Sca 1, by virtue of their lack of, or low level of, expression.

In a particularly preferred, non-limiting embodiment, a gene expression profile of a renal progenitor cell is defined as CD24a+cadherin l l+c-kit +/l°WSca- 1+noW CD34-.

In a seventh aspect, the invention provides use of metanephric mesenchyme cells, or more particularly renal progenitor cells, isolated or purified according to the invention, for in vitro and/or in vivo generation of renal tissue.

In an eighth aspect, the invention provides a nucleic acid array comprising a plurality of isolated nucleic acid molecules described herein, for use according to a method of any preceding aspect.

In a ninth aspect, the invention provides a protein array comprising a plurality of isolated protein molecules described herein, for use according to a method of any preceding aspect.

Preferably, according to the aforementioned aspects, the gene expression profile comprises a plurality of genetic markers, each of the genetic markers displaying at least 1.8 fold higher levels of expression in metanephric mesenchyme cells relative to intermediate mesenchyme cells.

Suitably, according to the aforementioned aspects, said metanephric mesenchyme cells, renal progenitor cells and/or renal stem cells are of mammalian origin.

Preferably, said metanephric mesenchyme cells, renal progenitor cells and/or renal stem cells are of human origin.

Suitably, according to the aforementioned aspects, said genetic markers are of mammalian origin.

Preferably, said genetic markers are of human origin.

Throughout this specification, unless otherwise indicated,"comprise", "comprises"and"comprising"are used inclusively rather than exclusively, so that a stated integer or group of integers may include one or more other non-stated integers or groups of integers.

BRIEF DESCRIPTION OF THE DRAWINGS In order that the present invention may be more readily understood and placed into practical effect, preferred embodiments of the invention will be described, by way of example only, with reference to the accompanying tables and figures, in which: TABLE 1: Classes of predicted membrane organization.

TABLE 2 : List of genes showing highest differential expression between intermediate mesoderm and metanephric mesenchyme at E10. 5 genes from NIA Microarrays according to a B-stat of >0 and a fold change >1. 8.

TABLE3 : List of genes showing highest differential expression between intermediate mesoderm and metanephric mesenchyme at E10. 5 genes from Compugen microarrays according to a B-stat of >0 and a fold change >1.8.

TABLE4 : Preferred markers of E10. 5 metanephric mesenchyme/renal progenitors based on data from Compugen and NIA chips taking into account fold change (>1. 8), B-stat (>0) and verification by in situ hybridisation.

TABLE 5 : Human gene equivalents of the mouse genes described in Table 4.

Human genetic markers are listed in corresponding order to the mouse genetic markers in Table 4. Human homologs of the mouse genetic markers were obtained using Homologene (available from the NCBI website: <BR> <BR> http : //www. ncbi. nlm. nih. gov/) or BLAST to compare two potential homologous full length cDNA sequences. In the case of murine CD24a, the human ortholog was identified at ENSML (http : //www. ensembl. orz/Homo_sapiens/geneview ? gene=ENSG00000185275) which lists human CD24 as the ortholog of murine CD24a antigen.

TABLE 6 : Expression of stem cell markers by renal progenitors in NIA microarray analysis.

FIG. 1. Analysis of microarray data. The three array comparison were normalised to each other to give a comparable range of log ratios. (A and B) Boxplot representations of the individual hybridisations before (A) and after (B) print-tip lowess normalisation. (C to E) Genespring scatterplots of each hybridisation. For replicate hybridisations (C and D), E10. 5 metanephric mesenchyme aRNA was labelled with Cy3 while E10. 5 intermediate mesoderm aRNA was labelled with Cy5. The sample labelling was reversed in a dye swap experiment to account for any dye bias (E). The outer lines represent 1. 80-fold differences in expression between samples. Spots located outside the lines were identified as outliers and used to generate lists of genes differentially expressed between samples. (F) Genes were ranked in decreasing order of the duplicate- correlated B-value, with the highest B-values indicating those with the most significant changes in expression level.

FIG. 2. RNA in situ hybridisation of genes differentially displayed between IM and MM at E10. 5 in the mouse. The expression pattern of each gene

was surveyed across E10. 5 embryos (A, E, I, M, Q, U, Y, c, g, k, o-Bars = 500 um, IM = intermediate mesoderm, HL = hind limb bud; B, F, J, N, R, V, Z, d, h, 1, p-Bars =100 um, ND = nephric duct, MM = metanephric mesenchyme, arrows represent budding site of primitive ureteric bud), E12. 5 urogenital tracts (C, G, K, O, S, W, a, e, i, m, q-Bars = 500 um, Ms = mesonephros, G = gonad, Mt = metanephros) and metanephric explants (D, H, L, P, T, X, b, f, j, n, r-Bars = 300 u. m). (A to D) Isletl, (E to H) Gata3, (I to L) Ewing sarcoma homolog, (M to P) p53, (Q to T) 14-3-3-theta, (U to X) Retinoic acid receptor alpha, (c to f) H19, (g to j) Stearoyl-coenzyme A desaturase 2, (k to n) Enolase and (o to r) RIKEN cDNA 1600029D21 gene.

FIG. 3. RNA in situ hybridisations of cell surface proteins representing renal progenitor cell markers. The expression pattern of each gene was surveyed across E10. 5 embryos (A, G, M, S, Y-Bars = 500 urn ; B, H, N, T, Z-Bars = 100 um, ND = nephric duct, MM = metanephric mesenchyme, arrows represent budding site of primitive ureteric bud), E12. 5 urogenital tracts (C, I, O, U, a- Bars = 500 lem), metanephric explants (D, J, P, V, b-Bars = 300 um ; E, K, Q, W, c-Bars = 50 um) and El 5. 5 kidney sections (F, L, R, X, d; Bars = 200 u. m). (A to F) Spint-2, (G to L) Claudin-6, (M to R) CD24a antigen, (S to X) Cadherin-11 and (Y to d) Hypothetical protein BG072310.

FIG. 4. Expression patterns of known stem cell markers during early kidney development. The expression pattern of each gene was analysed by RNA in situ hybridisation across E10. 5 embryos (A, E, I, M, Q, U, Y-Bars = 500 um ; B, F, J, N, R, V, Z-Bars = 100 u. m, ND = nephric duct, MM = metanephric mesenchyme, arrows represent budding sit of primitive ureteric bud), E12. 5 urogenital tracts (C, G, K, O, S, W, a-Bars = 500 um) and metanephric explants (D, H, L, P, T, X, b-Bars =300 um). (A to D) Oct-4, (E to H) Nanog, (I to L) CD34, (M to P) C-kit, (Q to T) Sca-1, (U to X) Podocalyxin-like and (Y to b) Nestin.

FIG. 5. Wholemount RNA iii situ hybridisation of genes enriched identified as enriched in E10. 5 MM from Compugen microarray analysis.

FIG. 6. In situ hybridisation analysis of CD24a and cadherin-11 throughout mouse kidney development.

FIG. 7. FACS analysis of embryonic and adult mouse kidneys for CD24a and cadherin-11 expressing cells demonstrating the presence of cell positive for both markers that decrease in population size over the course of kidney development. The presence of adult CD24a+cadherinll+ cells suggests the possibility of an adult renal progenitor or stem cell.

FIG. 8. CD24a expression in embryonic and adult mouse kidney side population cells (filled histogram) compared to isotype control (open histogram).

FIG. 9. Nucleotide sequences for each of the human genetic markers set forth in Table 5.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention is predicated, at least in part, by the present inventors'identification of differential gene expression by metanephric mesenchyme cells developing along a metanephric lineage or pathway.

Specifically, differential gene expression was observed for E10. 5 metanephric mesenchyme (MM) and intermediate mesoderm (IM) tissue. While both of these tissues are formed from adjacent mesoderm, only the committed but uninduced MM has the capacity to form kidney tissue and therefore comprises a renal progenitor population. The present invention provides 554 non-redundant genes that are differentially expressed in committed but uninduced metanephric mesenchyme (MM) compared to the surrounding intermediate mesoderm tissue at E10. 5. Of these, 51 non-redundant genes were found to encode transmembrane proteins expressed at the cell surface which could therefore be used both to identify and isolate renal progenitors. Gene expression profiles may therefore be used to identify, isolate and/or purify renal progenitor cells during renal differentiation or upon induction or production of renal progenitors from stem cells.

As used herein, the"Einbryonic day or E'stages of the mouse embryo development can be compared to the defined Theiler Stages, wherein E10. 5 corresponds to Theiler Stage 17. This corresponds to E32 in the developing

human embryo.

(http ://www. ana. ed. ac. uk/anatomy/database/humat/MouseComp. html).

It will be appreciated that the invention has initially been elucidated using a murine model of human kidney development. Accordingly, the invention described herein may advantageously be applied to human kidney development.

It will therefore be appreciated that the murine gene expression profiles described herein and the developmental stages that they are associated with in mice, will also apply to human renal development.

In this regard, the murine genetic markers identified herein as associated with metanephric mesenchyme and, in particular, renal progenitor cells, have human orthologs that may be readily utilized according to the invention in relation to human metanephric mesenchyme and, in particular, renal progenitor cells.

For the purposes of this invention, by"isolated"is meant material that has been removed from its natural state or otherwise been subjected to human manipulation. Isolated material may be substantially or essentially free from components that normally accompany it in its natural state, or may be manipulated so as to be in an artificial state together with components that normally accompany it in its natural state.

By"purified"and"purification", particularly in the context of cell purification from an initial cell population, is meant isolation of cells whereby the frequency or proportion of said cells in the isolated cell population is greater than in the initial cell population.

The term"gene"is used herein to describe a discrete, structural unit of a genome that may comprise one or more of introns, exons, open reading frames and regulatory sequences such as promoters and polyadenylation sequences.

As used herein a"gene expression profile"comprises one or more nucleic acid or protein products of gene expression (i. e genetic markers) that characterize a particular cell type and/or stage of development.

In one particular embodiment, a"gene expression profile"comprises one or more nucleic acid or protein products of gene expression that are differentially expressed by one or more metanephric mesenchyme cells compared to one or

more intermediate mesenchyme cells.

In another particular embodiment, a"gene expression profile"comprises one or more nucleic acid or protein products of gene expression that are differentially expressed by one or more metanephric mesenchyme cells at a particular stage of development compared to metanephric mesenchyme cells at one or more other stages of development.

An example is a gene expression profile of a renal progenitor cell or renal stem cell.

Thus, it will be appreciated that gene expression profiles do not necessarily relate to the presence or absence of gene expression or to quantitatively measuring absolute levels of gene expression, but typically relate to relative or differential levels of gene expression.

Typically, although not exclusively, a gene expression profile comprises a plurality of different nucleic acid or protein products of gene expression.

As set forth in Tables 2 and 3, a plurality of genetic markers have been identified, at least some of which may be used to establish a gene expression profile of MM cells compared to IM cells.

The genetic markers set forth in Tables 2 and 3 display at least 1.8 fold higher levels of expression in MM cells relative to IM cells.

However, it will be appreciated that genetic markers set forth in Tables 2 and 3 may display at least 2,3, 4, or 5-fold higher levels of expression in MM cells relative to IM cells.

As will be understood by persons of skill in the art, statistical analyses and in situ hybridization studies have been performed to establish the degree of reliability and/or reproducibility of the genetic markers identified in Tables 2 and 3.

Accordingly, Table 4 provides a list of murine genetic markers that have shown the highest reliability and/or reproducibility in terms of their association with MM cells compared to IM cells.

Table 5 provides a corresponding list of human genetic markers corresponding to the murine markers set forth in Table 4.

Human orthologs were identified using Homologene (available from the <BR> <BR> <BR> <BR> NCBI website: http : //www. ncbi. nlm. nih. gov/) or BLAST to compare two potential homolog fall length cDNA sequences. In the case of murine CD24a, ENSML (http ://www. ensembl. org/Homo sapiens/geneview ? gene=ENSG0000018 5275) was consulted, which identified human CD24 as the human ortholog of murine CD24a.

Preferably, the gene expression profile comprises one or more genetic markers selected from the group consisting of Zinc finger protein 335; Ewing sarcoma homolog; t-complex protein 1; enolase 1, alpha non-neuron; tyrosine 3- monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide (CDK5 regulatory subunit associated protein 2); Cytoplasmic FMR1 interacting protein 1 ; Sine oculis-related homeobox 2 homolog (Drosophila); Minichromosome maintenance deficient 7 (S. cerevisiae); Karyopherin (importin) alpha 2; Heat shock protein 8; Ras-GTPase-activating protein SH3-domain binding protein; Homeo box A10 ; Crystallin, mu; RIKEN cDNA 2610312E17 gene; Opioid growth factor receptor; Retinoic acid receptor alpha (RARa) ; Glial cell line derived neurotrophic factor; Mesoderm development candiate 2; RIKEN cDNA 1300010F03 gene; RIKEN cDNA 2810037C14 gene; Neuropilin-l ; CD164 antigen; CD83 antigen; Stromal cell derived factor receptor 1; CD24a antigen; Serine protease inhibitor, Kunitz type 2; Tumor-associated calcium signal transducer 1 ; Receptor-like tyrosine kinase; Fibroblast growth factor receptor 2; Amyloid beta (A4) precursor protein; Bone morphogenetic protein receptor, type 1A ; DNA segment, Chr 8, Wayne State University 49, expressed; Signal sequence receptor, alpha; Junction adhesion molecule 3; PTK7 protein tyrosine kinase 7; Cadherin 11; Syndecan binding protein; Integral membrane protein 2C; Tripartite motif-containing 59; NAD (P) dependent steroid dehydrogenase-like; Vesicle-associated membrane protein 3; DNA segment, Chr 3, University of California at Los Angeles 1; Solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2; RIKEN cDNA 1110018G07 gene; Purine rich element binding protein B; Solute carrier family 6 (neurotransmitter transporter, taurine), member 6; Gap junction membrane

channel protein alpha 1; Tumor differentially expressed 1; CD81 antigen; Solute carrier family 35, member F5; Solute carrier family 39 (zinc transporter), member 7; Gene rich cluster, C3f gene; Claudin 6; Solute carrier family 20, member 1; Solute carrier family 16 (monocarboxylic acid transporters), member 1 ; ADP- ribosylation factor-like 6 interacting protein 2; Autocrine motility factor receptor; Claudin 7; Calcitonin receptor-like; Tumor differentially expressed 2; Synaptophysin-like protein; Claudin 11; G protein-coupled receptor 89 ; ELOVL family member 6, elongation of long chain fatty acids (yeast); Purinergic receptor (family A group 5); Non imprinted in Prader-Willi/Angelman syndrome 2 homolog (human); RIKEN cDNA 4930579A11 gene; RIKEN cDNA 2610311119 gene; Zinc finger, DHHC domain containing 6; Solute carrier family 37 (glycerol- 3-phosphate transporter), member 3; Sarcoma amplified sequence; RIKEN cDNA 1700022N24 gene; Mid-l-related chloride channel 1; Stearoyl-Coenzyme A desaturase 2; RIKEN cDNA 1110034A24 gene; Homeo box D13; retinol dehydrogenase 10 (all-trans) (RdhlO) ; Sal-like 4 (Drosophila); Homeo box All, opposite strand transcript; and Roundabout homolog 2 (Drosophila).

As set forth in FIG. 9, examples of human nucleotide sequences corresponding to each of the genetic markers in Table 5.

For the purposes of cell isolation and/or purification, the invention contemplates particular use of genetic markers in the form of one or more proteins expressed at the cell surface of a metanephric mesenchyme cell, inclusive or renal progenitor cells and renal stem cells.

With this in mind, Table 1 sets forth a classification of proteins that provides a code that is used in Tables 2-4.

According to this code, preferred cell surface proteins are selected from the group consisting of : Neuropilin-l ; CD164 antigen; CD83 antigen; Stromal cell derived factor receptor 1; CD24a antigen; Serine protease inhibitor, Kunitz type 2; Tumor-associated calcium signal transducer 1; Receptor-like tyrosine kinase; Fibroblast growth factor receptor 2; Amyloid beta (A4) precursor protein; Bone morphogenetic protein receptor, type 1A ; DNA segment, Chr 8, Wayne State University 49, expressed; Signal sequence receptor, alpha; Junction adhesion molecule 3; PTK7 protein tyrosine kinase 7; Cadherin 11; Syndecan binding

protein; Integral membrane protein 2C; Tripartite motif-containing 59; NAD (P) dependent steroid dehydrogenase-like; DNA segment, Chr 3, University of California at Los Angeles 1 ; Solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2; RIKEN cDNA 1110018G07 gene; Purine rich element binding protein B; Solute carrier family 6 (neurotransmitter transporter, taurine), member 6; Gap junction membrane channel protein alpha 1 ; Tumor differentially expressed 1; CD81 antigen; Solute carrier family 35, member 5; Solute carrier family 39 (zinc transporter), member 7; Gene rich cluster, C3f gene ; Claudin 6; Solute carrier family 20, member 1; Solute carrier family 16 (monocarboxylic acid transporters), member 1; ADP-ribosylation factor-like 6 interacting protein 2; Autocrine motility factor receptor; Claudin 7; Calcitonin receptor-like; Tumor differentially expressed 2; Synaptophysin-like protein; Claudin 11; G protein-coupled receptor 89; ELOVL family member 6 (Elovl6), elongation of long chain fatty acids (yeast); Purinergic receptor (family A group 5); Non imprinted in Prader-Willi/Angelman syndrome 2 homolog (human); RIKEN cDNA 4930579A11 gene; Zinc finger, DHHC domain containing 6; Solute carrier family 37 (glycerol-3-phosphate transporter), member 3; Sarcoma amplified sequence; RIKEN cDNA 1700022N24 gene; and Mid-1- related chloride channel 1.

Although not wishing to be bound by any particular theory, the present invention postulates that genetic markers differentially expressed by metanephric mesenchyme cells in earlier stages of development compared to later stages may be genetic markers associated with renal progenitors and thereby facilitate their identification and isolation with respect to other metanephric mesenchyme cells.

While the invention as described herein makes reference to genetic markers set forth variously in Tables 2-5 and FIG. 9, it will also be appreciated that the invention provides a principle capable of general application to the identification of other genetic markers that may be indicative of, or otherwise associated with metanephric mesenchyme development and, more particularly, renal progenitors inclusive of renal stem cells.

A particular feature of the invention is the identification and use of gene expression profiles for the identification, isolation and/or purification of renal

progenitor cells and/or renal stem cells. It is postulated that renal progenitor cells may comprise renal stem cells.

As used herein, a"renal progenitor cell"is a metanephric mesenchyme cell which is a developmental antecedent of one or more mature renal cell types.

This definition does not exclude the possibility that renal progenitor cells in later stages of the developing kidney may have the same phenotype as those defined in the metanephric mesenchyme.

As used herein, a"stem cell"is a progenitor cell capable of self-renewal and differentiation into one or more mature cell types.

As used herein, a"renal stem cell"is a progenitor cell capable of self- renewal and differentiation into one or more mature renal cell types.

It will be appreciated that stem cells may be embryonic stem cells or adult stem cells.

In a particularly advantageous form, the invention provides a gene expression profile of a renal progenitor cell in the form of a cell surface marker profile.

This profile may comprise cell surface markers as hereinbefore identified together with one or more other stem cell markers as described in Table 6.

Preferably, the one or more other stem cell markers are selected from the group consisting of CD34, c-kit and Sca 1, by virtue of their lack of, or low level of, expression.

In a particular, non-limiting embodiment the cell surface marker profile of a renal progenitor cell is set forth as CD24a+cadherin ll+c-kit +/l°wSca-l+/l°w <BR> <BR> <BR> <BR> CD34-.<BR> <BR> <BR> <BR> <BR> <BR> <BR> <P> Nucleic acid based deterenination of gene expression In particular embodiments of the present invention, gene expression profiles of metanephric mesenchyme, inclusive of renal progenitor cells and stem cells, may be determined by methods that employ nucleic acid detection.

Typically, such methods use gene-specific primers and/or probes for nucleic acid detection and include but are not limited to, nucleic acid arrays (in microarrays), nucleic acid sequence amplification and blotting techniques.

For the purposes of determining one or more gene expression profiles of temporal stages of metanephric mesenchyme development, the invention contemplates particular embodiments of such methods which may be used alone or in combination.

Generally, these methods of the invention measure nucleic acid expression levels of intermediate mesenchyme and metanephric mesenchyme cells or tissues.

The term"nucleic acid"as used herein designates single-or double-stranded mRNA, RNA, cRNA and DNA, said DNA inclusive of cDNA and genomic DNA.

A"probe"may be a single or double-stranded oligonucleotide or polynucleotide.

A"primer"is usually a single-stranded oligonucleotide, preferably having 15-50 contiguous nucleotides, which is capable of annealing to a complementary nucleic acid"template"and being extended in a template-dependent fashion by the action of a DNA polymerase such as Taq polymerase, RNA-dependent DNA polymerase or Sequenase.

It will also be appreciated that probes and/or primers may be labelled for the purpose of detecting amplification products and/or complementary sequences by hybridization and other uses as is well known in the art.

The terms"hybridize and hybridization"are used herein to denote the pairing of at least partly complementary nucleotide sequences to produce a DNA- DNA, RNA-RNA or DNA-RNA hybrid. Hybrid sequences comprising complementary nucleotide sequences occur through base-pairing between complementary purine and pyrimidine bases, or between modified purines (for example, inosine, methylinosine and methyladenosine) and modified pyrimidines (for example thiouridine and methylcytosine).

In particular, non-limiting embodiments, the invention contemplates use of one or more molecular makers set forth in any one of Tables 2,3, 4 and/or 5, in nucleic acid form, for identification, isolation and/or purification of MM cells and/or renal progenitor cells inclusive of renal stem cells.

More particularly, examples of human nucleic acid sequences are provided in Table 5 which may be utilized according to the invention.

It will be appreciated that fragments of the aforementioned nucleic acid markers may be utilized, such as primers for nucleic acid sequence amplification and/or as probes for nucleic acid hybridization, although without limitation thereto.

Nucleic acid' ! fragments" may preferably comprise at least 20 contiguous nucleotides and up to 50,100, 200,300, 500 or more contiguous nucleotides, as required.

According to the invention, a nucleic acid amplification technique may include polymerase chain reaction (PCR) and ligase chain reaction (LCR) as for example described in Chapter 15 of Ausubel et al. supra; strand displacement amplification (SDA) as for example described in U. S. Patent No 5,422, 252; rolling circle replication (RCR) as for example described in Liu et al., 1996, J.

Am. Chem. Soc. 118 1587 and International application WO 92/01813, and Lizardi et al., (International Application WO 97/19193); nucleic acid sequence- based amplification (NASBA) as for example described by Sooknanan et al., 1994, Biotechniques 17 1077; ligase chain reaction (LCR) as for example described in International Application W089/09385 ; Q-ß replicase amplification as for example described by Tyagi et al., 1996, Proc. Natl. Acad. Sci. USA 93 5395 and helicase-dependent amplification as for example described in International Publication WO 2004/02025.

As used herein, an"ampliJ2cation refers to a nucleic acid product generated by any nucleic acid amplification technique.

In another particular form, quantitative PCR using primers corresponding to one or more genes expressed by MM or IM cells of particular stages of development may be used to quantify relative expression levels of one or many nucleic acids to thereby determine the relative gene expression for each MM or IM tissue.

In a particular, non-limiting embodiment described in more detail hereinafter, expressed RNA is linearly amplified using a messageAMP to provide "aRNA"kit supplied by Ambion.

Preferably, according to this embodiment, the aRNA is reverse transcribed using random hexamers (Promega) into cDNA incorporating either Cy5-or Cy3- labelled dUTPs (Amersham).

Nucleic acid arrays provide a particularly advantageous method of initially identifying or establishing a gene expression profile of a particular stage of metanephric mesenchyme development and also for subsequent detection of a gene expression profile when determining the stage of development of metanephric mesenchyme cells.

Nucleic acid arrays typically use libraries of genomic DNA or cDNA.

In one particular form, the invention provides a molecular library in the form of a nucleic acid array that comprises a substrate to which is immobilized, bound or otherwise coupled a plurality of nucleic acids that correspond to the expressed genes that are characteristic of a particular stage of metanephric mesenchyme development, or respective fragments thereof. Each immobilized, bound or otherwise coupled nucleic acid has an"address"on the array that signifies the location and identity of said nucleic acid.

Generally, nucleic acid array technology has become well known in the art and examples of methods applicable to array technology are provided in Chapter 22 of CURRENT PROTOCOLS IN MOLECULAR BIOLOGY Eds. Ausubel et al. (John Wiley & Sons NY USA 1995-2001).

The array can have a density of at least 10,50, 100,200, 500,1, 000, 2,000, or 10,000 or more addresses/cm2, and ranges there between. The substrate may be a two-dimensional substrate such as a glass slide, a wafer (e. g. , silica or plastic), a mass spectroscopy plate, or a three-dimensional substrate such as a gel pad. Addresses in addition to the 15K mouse clone set of nucleic acids of the invention may also be disposed on the array.

In certain embodiments, at least one address of the plurality includes a nucleic acid capture probe that hybridizes specifically to a member of a nucleic acid library, e. g. , the sense or anti-sense strand. In one preferred embodiment, a subset of addresses of the plurality of addresses has a nucleic acid capture probe for a nucleic acid library member. Each address of the subset can include a capture probe that hybridizes to a different region of a library member.

An array format may comprise glass slides having an immobilized, ordered grid of a plurality of cDNA fragments.

In particular embodiments, said array has 5,000 to 19,000 or up to 40,000 cDNA fragments.

Preferably, each said cDNA fragment corresponds to a particular gene or expressed sequence tag (EST) gene fragment.

An array can be generated by various methods, e. g., by photolithographic methods (see, e. g., U. S. Patent Nos. 5,143, 854; 5,510, 270; and 5,527, 681), mechanical methods (e. g., directed-flow methods as described in U. S. Patent No.

5,384, 261), pin-based methods (e. g., as described in U. S. Pat. No. 5,288, 514), and bead-based techniques (e. g., as described in PCT US/93/04145).

In a preferred embodiment described in more detail hereinafter, nucleic acid arrays were performed using chips arrayed with the National Institute of Health-National Institute of Aging 15K mouse cDNA clone set (http ://lgsun. grc. nia. nih. gov/cDNA/15k. html) in addition to a selection of custom clones submitted from the Institute for Molecular Bioscience (University of Queensland, Brisbane) and contained 15,989 elements in total (SRC NIA v3.0 chips).

The National Institute of Ageing (NIA) array is a 15K mouse clone set containing 15,247 expressed sequence tags (ESTs) derived from pre-and periimplantation embryo E12.5 female gonad/mesonephros and newborn ovary cDNA libraries.

The Compugen long oligonucleotide set used to create the additional Compugen lists are commercially available (http : //www. labonweb. com/chips/libraries. html). Other human sets may be obtained from Agilent (for long oligonucleotides), Affymetrix (for short oligonucleotides synthesized on a substrate) or cDNA microarrays as produced by the Ontario Cancer Institute (http://www. oci. utoronto. ca/services/microarray/).

In a preferred embodiment, gene expression is measured by isolating mRNA from samples MM and IM tissue and comparing expression with that of another sample (e. g. MM tissue of a different development stage or surrounding IM tissue).

Other known conventional identification methods are contemplated.

Typically, complementary nucleotide sequences are identified by blotting techniques that include a step whereby nucleotides are immobilized on a matrix (preferably a synthetic membrane such as nitrocellulose), a hybridization step, and a detection step (eg. northern hybridization). Dot blotting and slot blotting can be used to identify complementary RNA/RNA, DNA/RNA or DNA/DNA polynucleotide sequences. Such techniques are well known by those skilled in the art, and have been described in Ausubel et al., supra, at pages 2.9. 1 through 2.9. 20.

Methods for detecting labelled nucleic acids hybridized to an immobilized nucleic acid are well known to practitioners in the art. Such methods include autoradiography, chemiluminescent, fluorescent and colorimetric detection.

In particular embodiments, genes identified in Tables 2 and 3 may be used to determine whether a subpopulation of metanephric mesenchyme cells or stem cells from a variety of sources, including embryonic and adult stem cells from human tissues, is or has been, induced to become a renal progenitor based upon expression of one or more of these genes.

This can be assessed in a variety of ways, including but not limited RT- PCR, Northern analysis and/or in situ hybridisation, such as hereinbefore described.

Protein based deterinination of geiie expression and cellpurification Gene expression profiles of metanephric mesenchyme, inclusive of renal progenitor cells and stem cells may be determined by methods that employ protein detection.

Protein-based methods are also particularly useful for cell isolation and purification according to cell surface protein expression.

By"protein"is meant an amino acid polymer. The amino acids may be natural or non-natural amino acids, D-or L-amino acids as are well understood in the art.

As used herein,"protein"includes full-length proteins and fragments thereof including but not limited to, peptides, peptide-nucleic acid conjugates and

epitopes capable of being recognized, bound or otherwise detected by an antibody.

In one embodiment, identification of a gene expression profile may be performed using protein libraries or arrays.

For example, a plurality of proteins may be used in a protein library displayed in any of a number of ways, e. g., in phage display or cell display systems, in protein arrays or by two-dimensional gel electrophoresis, or more specifically, differential two-dimensional gel electrophoresis (2D-DIGE). These particular embodiments may generally be referred to as'proteomic"or"protein profiling"methods, such as described in Chapters 3.9. 1 and 22 of CURRENT PROTOCOLS IN PROTEIN SCIENCE Eds. Coligan et al., John Wiley & Sons NY USA (1996-2002). Other particular examples include the SELDI protein chip technology of Ciphergen (www. Ciphergen. com/doclib/docFiles/262).

In embodiments relating to protein arrays, preferably each of a plurality of expressed proteins of the invention is located at an identifiable address on the array.

Preferably, the protein array comprises a substrate to which is immobilized, impregnated, bound or otherwise coupled a plurality of proteins described herein, or respective fragments thereof. Each immobilized, impregnated bound or otherwise coupled protein is at an"address"on the array that signifies the location and identity of each said protein.

The substrate may be a chemically-derivatized aluminium chip, a synthetic membrane such as PVDF or nitrocellulose, a glass slide or microtiter plates.

Detection of substrate-bound proteins may be performed using known methods such as mass spectrometry, ELISA, immunohistochemistry, fluorescence microscopy or colorimetric detection.

Determination of protein expression may also conveniently be performed using antibodies or antibody fragments (such as Fab and Fab2 fragments) directed to one or more proteins of a particular gene expression profile.

These antibody-based methods may have particular efficacy in isolation and purification of renal progenitor cells.

Typically, the antibody or antibody fragment further comprises a label.

The label may be selected from a group including a chromogen, a catalyst, an enzyme, a fluorophore, a chemiluminescent molecule, a lanthanide ion such as Europium (Eu34), a radioisotope (e. g. 125I) and a direct visual label. In the case of a direct visual label, use may be made of a colloidal metallic or non-metallic particle, a dye particle, an enzyme or a substrate, an organic polymer, a latex particle, a liposome, or other vesicle containing a signal producing substance and the like.

A large number of enzymes useful as labels is disclosed in United States Patent Specifications U. S. 4,366, 241, U. S. 4,843, 000, and U. S. 4,849, 338, all of which are herein incorporated by reference. Enzyme labels useful in the present invention include alkaline phosphatase, horseradish peroxidase, luciferase, ß- galactosidase, glucose oxidase, lysozyme, malate dehydrogenase and the like.

The enzyme label may be used alone or in combination with a second enzyme in solution.

By way of example, the fluorophore may be fluorescein isothiocyanate (FITC), oregon green, tetramethylrhodamine isothiocyanate (TRITL), allophycocyanin (APC), R-Phycoerythrin (RPE), Cy3 and/or Cy5 although without limitation thereto.

In a preferred embodiment, particularly with regard to the isolation and purification of metanephric mesenchyme and/or renal progenitor cells per se from metanephric mesenchyme, one or more antibodies are used in conjunction with a cell isolation technique such as any technique that selects cells (i. e positive selection) or depletes cells (i. e negative selection) according to cell surface protein expression.

A non-exhaustive list includes panning, complement-mediated lysis, fluorescence-activated cell sorting (FACS) and magnetic activated cell sorting (MACS).

For FACS enrichment, fluorescently-labelled antibodies are bound to the cells of interest. These cells are then passed through the excitation laser in a single cell stream and measured for size, granularity and fluorescent activity.

Specific parameters are set and cells that fall within those parameters (e. g. fluorescence, forward light scatter, side scatter) are collected by a cell sorter.

For MACS enrichment, monoclonal antibodies coupled to small magnetic particles are bound to the cells of interest. Using a magnet, the bound cells may be enriched from contaminating cells. Alternatively, contaminating cells may be removed with bound beads.

Protein based detection of gene expression profiles according to the invention may also utilize immunoassays, for example ELISA, immunohistochemistry or immunoblotting to detect relative expression levels of one or more proteins to determine the stage of metanephric mesenchyme development.

With regard to appropriate cell surface protein for use according to the invention, Tables 2 and 3 identify genetic markers that are, or are likely to be, expressed at the cell surface.

Referring to Table 4 and Table 5, a preferred group of cell surface markers include Neuropilin-1 (Nrpl) ; CD164 antigen; CD83 antigen (CD83); Stromal cell derived factor receptor 1; CD24a antigen; Serine protease inhibitor, Kunitz type 2 (Spint-2); Tumor-associated calcium signal transducer 1 ; Receptor-like tyrosine kinase; Fibroblast growth factor receptor 2; Amyloid beta (A4) precursor protein; Bone morphogenetic protein receptor, type 1A; DNA segment, Chr 8, Wayne State University 49, expressed; Signal sequence receptor, alpha; Junction adhesion molecule 3; PTK7 protein tyrosine kinase 7; Cadherin 11; Syndecan binding protein; Integral membrane protein 2C; Tripartite motif-containing 59; NAD (P) dependent steroid dehydrogenase-like; DNA segment, Chr 3, University of California at Los Angeles 1; Solute carrier family 3 (activators of dibasic and neutral amino acid transport), member 2; RIKEN cDNA 1110018G07 gene; Purine rich element binding protein B (purb); Solute carrier family 6 (neurotransmitter transporter, taurine), member 6; Gap junction membrane channel protein alpha 1; Tumor differentially expressed 1 ; CD81 antigen; Solute carrier family 35, member F5; Solute carrier family 39 (zinc transporter), member 7; Gene rich cluster, C3f gene; Claudin 6; Solute carrier family 20, member 1; Solute carrier family 16 (monocarboxylic acid transporters), member 1 ; ADP-

ribosylation factor-like 6 interacting protein 2; Autocrine motility factor receptor; Claudin 7; Calcitonin receptor-like; Tumor differentially expressed 2; Synaptophysin-like protein; Claudin 11; G protein-coupled receptor 89; ELOVL family member 6, elongation of long chain fatty acids (yeast); Purinergic receptor (family A group 5) ; Non imprinted in Prader-Willi/Angelman syndrome 2 homolog (human); RIKEN cDNA 4930579A11 gene; Zinc finger, DHHC domain containing 6 ; Solute carrier family 37 (glycerol-3-phosphate transporter), member 3; Sarcoma amplified sequence; RIKEN cDNA 1700022N24 gene ; and Mid-1- related chloride channel 1, although without limitation thereto, either singly or in combination.

In this regard, a gene expression profile particularly associated with renal progenitors and potentially renal stem cells is defined as CD24a+cadherin 11+c-kit Sca-lCD34-.

It will be appreciated with reference to Table 6 that CD34, Sca-1 and c-kit are additional cell surface markers that may be used with one or more of the genetic markers described herein that facilitate identification, isolation and/or purification of renal progenitors, inclusive of renal stem cells by virtue of their lack of, or low level of, expression.

Antibodies to the aforementioned cell surface markers are readily available commercially, either alone or conjugated to fluorochromes as hereinbefore described.

It is also well within the scope of a person skilled in the art to produce antibodies by immunization of a production species (such as rabbits, mice, rats etc) to produce monoclonal or polyclonal antibodies according to standard methods in the art.

Uses of isolated atidlorpurified rerialprogenitor cells In light of the foregoing, the skilled addressee will appreciate that the renal progenitor cells and renal stem cells purified according to the invention may find therapeutic use as adjunct therapy in the renal transplant procedures.

The skilled person may further appreciate that any source of embryonic or adult stem cell (eg. human embryonic stem cell, neural stem cell, haematopoietic stem cell, mesodermal stem cell) could be induced towards a mesodermal lineage

using co-culture with growth factors or conditioned medias. There are a number of mesodermal fates they may adopt, including muscle, bone, cartilage or haematopoietic cells. Hence the expression of the cell markers may find utility in demonstrating which stem cells had adopted or were adopting a renal fate.

The skilled person may also appreciate the combination of cell surface markers which together define the renal progenitors allows antibodies to these cell surface markers to be used to enrich, purify and isolate specific subpopulations of renal progenitors. This aspect of the invention provides utility in isolating renal progenitor cells from mixed populations in which some subpopulations adopt a renal fate and others do not.

It will be appreciated that the above markers may also be used to identify and then isolate adult renal stem cell or progenitor populations from an adult kidney.

It will be appreciated to the skilled person that the isolated progenitor cells may be used in adjunct therapy. Specifically, the progenitor cells may be introduced into the renal parenchyma of the kidney or the renal capsule to elicit repair. They may further be introduced via the generalised or renal vasculature, which may involve injection into the renal artery. Any introduction of renal progenitor cells may be accompanied by an adjunct insult or stress to the kidney, such as mild ischaemia or radiation or other stresses designed to stimulate the receptivity of the kidney. Introduction of renal progenitor cells may include growth factors, cytokine or other agents selected to stimulate the integration and onward differentiation of renal progenitors into the receiving kidney or reduce the rejection of the progenitor cells by the receiving kidney. They may further be used in combination with biomatrices and growth factors to generate a replacement kidney organ de novo. The process of metanephric transplantation, where embryonic kidney is grown in the peritoneal cavity of a recipient animal may utilize methodology as previously described (Dekel et al., 2003, Nat. Med. 9 53-60; Hammerman, 2003, Nephron Exp. Nephrol. 2003,93 e58; Hammerman, 2003, Kidney Int. 63 1195-1204; Hammerman, 2000, Pediatr. Nephrol. 14 513- 517).

In this regard, reference is also made to International Publication W02004/090112 which describes examples of methodologies that may be utilized for treating acute renal failure, kidney transplant dysfunction and chronic renal failure by administration of kidney precursor cells to a patient. The present invention provides a particularly advantageous method and set of molecular markers whereby renal progenitors may be isolated and/or purified for use in vivo to treat diseases or conditions such as acute renal failure, kidney transplant dysfunction and/or chronic renal failure.

In order that the invention may be readily understood and put into practical effect, particular embodiments will now be described by way of the following non-limiting examples.

EXAMPLES The two main goals of this invention were (1) to identify the earliest markers of commitment to renal differentiation and (2) to determine the cell surface molecule phenotype of renal progenitor cells. The microarray expression profile of the uninduced MM from E10. 5 mice was examined by comparison to adjacent rostral IM, comprising the portion of the nephrogenic cord containing the mesonephros and which will give rise to the genital ridge. In this way, markers identifying the MM from UB and surrounding IM at the point of MM commitment were determined. We refer to the committed, undifferentiated MM as the renal progenitor timepoint.

EXAMPLE 1 Idefztification of molecular markers of uszinduced ssaesodermal mesefzclzyfrze Materials and Methods Tissue Collection and RNA Isolation Naturally mated outbred female CD1 mice were culled by cervical dislocation (Animal ethics committee approval number IMB/479/02/NIH) at embryonic day (E) 10.5. MM and rostral IM tissue (nephrogenic cord including mesonephros and genital ridge) was dissected from E10. 5 embryos and snap- frozen on dry ice. Embryos were defined as E10. 5 by the presence of between 8 and 10 tail somites. Pooled tissue was stored at-80 °C. Dissections were performed in cold phosphate-buffered saline (PBS). Total RNA was prepared

using Trizoll (GibcoBRL) extraction in combination with RNeasy mini kits (Qiagen).

Expression profiling using NIA microarrays Total RNA was linearly amplified using the messageAMP aRNA kit (Ambion). Briefly, 1000 nanograms of total RNA was reverse transcribed into cDNA using a T7 promoter-dT primer and amplified through an in vitro transcription reaction (12 hours) using T7 RNA polymerase to produce antisense RNA (aRNA). The aRNA was reverse transcribed using random hexamers (Promega) into cDNA incorporating either Cy5-or Cy3-labelled dUTPs (Amersham). Labelled targets were hybridised to microarray chips for 16 hours at 45°C.

Arrays were produced by the SRC Microarray Facility, University of Queensland (ARC Centre for Functional and Applied Genomics). Experiments were performed using chips arrayed with the National Institute of Health- National Institute of Aging (NIA) 15K mouse cDNA clone set (http ://lgsun. grc. nia. nih. gov/cDNA/15k. html) in addition to a selection of custom clones submitted from the Institute for Molecular Bioscience (University of Queensland, Brisbane) and contained 15,989 elements in total (SRC NIA v3.0 chips). Every element was spotted in duplicate on each chip. The NIA 15K mouse clone set contained 15,247 expressed sequence tags (ESTs) derived from pre-and peri-implantation embryo, E12.5 female gonad/mesonephros and newborn ovary cDNA libraries (Tanaka et al., 2000, Proc. Natl. Acad. Sci. USA 97 9127-9132) thus making it an ideal gene set for this experiment. 14,428 of these ESTs sequences map to Unigene/TIGR/Ensembl and represent 11834 distinct transcripts after removal of duplicates. Up to 50% of clones were derived from novel genes.

Hybridised slides were scanned with a GMS 418 array scanner (Genetic MicroSystems) and images were analysed with Imagene 5.5 (Biodiscovery). The microarray data was analysed with R statistical software using the LIMMA package (http ://bioinf. wehi. edu. au/limma/) with scripts developed by Ola Spjuth of the Linnaeus Centre for Bioinformatics (http://www. lcb. uu. se/baseplugins. php). Mean foreground signals were taken for

each spot and nonnalised within each array using print-tip lowess without background correction to give a mean value of zero for the log ratios of the two channels within each print block. The final normalise values were use for B- statistics calculations. B-statistics analysis included an allowance for the correlation between adjacent duplicate spots printed on the same array. A threshold B-score >0 was used to define differential expression. Normalised data were imported into Genespring 6.1 (Silicon Genetics) to generate lists of differentially expressed genes. All microarray data, protocols and lists of differentially expressed genes are available for download from the following website: http://kidney. scgap. org/base/index. phtml.

Expression profiling using Compugen Microarray Analysis Compugen (CGEN) chips contained the Compugen 22K mouse set of 65- mer oligonucleotides (http ://www. labonweb. com/chips/libraries. html) and contained 22,329 elements in total. Total RNA was linearly amplified using the Amino Allyl messageAMP aRNA kit (Ambion). Briefly, 1000 nanograms of total RNA was reverse transcribed into cDNA using a T7 promoter-dT primer and amplified through an in vitro transcription reaction (12 hours) using T7 RNA polymerase to produce antisense RNA (aRNA). 5- (3-aminoallyl)-UTP was incorporated into the aRNA during in vitro transcription. A dye-coupling reaction was used to conjugate the amino allyl modified aRNA to mono-reactive NHS esters of either Cy3 or Cy5 moeities (Amersham). Labelled targets were hybridised to microarray chips for 16 hours at 42°C. Each array experiment was repeated in duplicate and included a dye reversal experiment to account for any dye bias. Hybridised slides were scanned with a GMS 418 array scanner (Genetic MicroSystems) and images were analysed with Imagene 5.5 (Biodiscovery). The microarray data was analysed with R statistical software using the LIMMA package (http ://bioinf. wehi. edu. au/limma/) with scripts developed by Ola Spjuth of the Linnaeus Centre for Bioinformatics (http://www. lcb. uu. se/baseplugins. php). Mean foreground signals were taken for each spot and normalised within each array using print-tip lowess without background correction to give a mean value of zero for the log ratios of the two channels within each print block. The final normalised values were used for B-

statistics calculations as summarised in Table 3. B-statistics analysis included an allowance for the correlation between adjacent duplicate spots printed on the same array. A threshold B-score >0 was used to define differential expression.

Normalised data were imported into Genespring 6.1 (Silicon Genetics) to generate lists of differentially expressed genes. Table 5 shows a subset of Table 3 whereby 35 non-redundant elements with a B-score >0 were shown to have an average increase in differential expression >1. 80-fold greater in the uninduced MM compared to the surrounding IM.

Bioinformatics and membrane organization predictions Representative sequences for differentially expressed ESTs or oligonucleotides were extracted from the National Centre for Biotechnology Information (NCBI) database (http ://www. ncbi. nlm. nih. gov/). Using BLAST (Altshul et al., 1990, J. Mol. Biol. , 215 403-410) each NIA EST sequence was mapped to an identical full-length RIKEN representative transcript/protein sequence (RIKEN RTPS 6.3 set). The RIKEN RTPS 6.3 set was recently annotated using a number of bioinformatic approaches (Kanapin et al., 2003, Gen. Res. 13 1335-1344) including the prediction of the membrane organisation of individual full-length proteins into one of six categories based on the presence or absence of endoplasmic reticulum-retention signal peptides and helical transmembrane (Table 1).

Metanephric Culture and Tissue Preparation For RNA in situ hybridisation, embryos were collected from outbred CD1 mice as above at days 10.5, 12.5 and 15.5 of gestation. E10. 5 embryos were cut transversely below the forelimbs and longitudinally down the midline to expose the ND, UB and MM. At E12.5, complete urogenital (UG) tracts were collected.

For section RNA in situ analyses, metanephroi from El 5. 5 embryos were dissected as above and fixed in 4% paraformaldehyde (PFA) in PBS for 2 hours at 4°C. Tissue was processed and embedded in paraffin. Sections were cut at 7 pm.

For explant culture, metanephroi were isolated from E12. 0 embryos and grown as explants for two days at 5% CO2, 37°C on 3.0 urn polycarbonate transwell filters (Costar) in minimum essential medium (MEM) supplemented with 10% fetal calf

serum (FCS) and 20mM glutamine. Tissue for whole mount in situ hybridisation was fixed overnight in 4% PFA/PBS at 4°C.

RNA in situ hybridisation Expression patterns were analysed by RNA in situ hybridisation using digoxigenin-labelled sense and antisense riboprobes. Probes were synthesized as described previously (Holmes et al., 1998, Mech. Dev. 79 57-72) using pSPORTl constructs containing the NIA EST of interest (SRC Microarray facility). Probes were not fragmented by hydrolysis and were purified using Sephadex columns (Roche) following digestion of the vector with DNaseI (Promega) for 15 minutes at 37°C. Whole mount in situ hybridizations were performed as described by (Christiansen et al., Mech. Dev. 51 341-350) with minor modifications. All probes were hybridised at 65°C and post-antibody washes reduced to 30 minutes.

Tissue was mounted in Mount-Quick aqueous (Daido Sangyo) and photographs were taken using an Olympus AX70 compound microscope with Kodak Elite Ektachrome 160T colour reversal film. Section in situ hybridisations were hybridised at 65°C and post-hybridisation processing was performed using DIG wash and block buffer set (Roche). Sections were mounted in Mount-Quick (Daido Sangyo) and photographs were taken as above.

Results Summary of Gene Expression Profile Analysis Until recently, it has been difficult to perform meaningful expression profile studies in embryological systems due to the limiting amount of nucleic acid available from small amounts of tissue. This problem was circumvented in this study by using mRNA linear amplification to produce amplified RNA (aRNA). aRNA produced by in vitro transcription has been shown to have a correlation coefficient >0.95 to total RNA and aRNA produced using different amounts of template total RNA (Luo et al., 1999, Nat. Med. 5 117-122; Baugh et al., Nucl. Acid Res. 25 e29). To minimise nonlinearity and ensure consistency, all samples were amplified under the exact same conditions at the same time.

All array experiments were performed in duplicate and included a dye reversal experiment to account for any dye bias and the three arrays were normalised to each other to give a comparable range of log ratios. The scatter and

volcano plots of the NIA expression profiling are provided as an example of data quality in Figure 1. The raw data for both NIA and Compugen expression profiling can be accessed via the webmaster at kidney. scgap. org. The skilled person will know that this data can be analysed in R tools, Genespring or other expression profiling software and a list of genes differentially expressed in the E10. 5 MM versus the adjacent IM determined based upon a variety of stringency criteria. Thee criteria might include fold change or statistical score (B-stat) or a combination of the two. Our preferred method of analysis is to take into account both B-stat and fold change. The data listed in Tables 2 and 3 represent a subset of the genes enriched in MM using either the NIA or Compugen gene sets. This includes all genes in which the fold change was greater than 1.8 fold and the B- stat was greater than 0. Both B-stat and fold change are indicated. A total of 26 genes from NIA and 528 genes from Compugen are detailed in Tables 2 and 3.

Hence, this set comprises 554 markers.

The sequence of each differentially expressed EST or Compugen oligo was mapped to a full-length protein sequence from the RIKEN RTPS 6.3 set and the membrane organisation predictions were adopted for each gene of interest. Of particular interest were candidate genes from class C (type I membrane proteins), class D (type II membrane proteins) and class E (multi-span membrane proteins) for their potential utility in antibody-based fluorescence-activated cell sorting (FACS) for the purification of renal progenitors.

Molecules Determifaing the Renal Progenitor Phenotype The temporospatial expression patterns of genes in Tables 2-4, most preferably Table 4, were determined using RNA in situ hybridisation (Figures 2- 6). Wholemount RNA in situ analysis (WISH) at E10. 5 and E12. 5 indicates that a proportion of genes identified using expression profiling were validated as MM- specific using WISH. In some cases, such as Islet 1 and Gata3, this was not shown to be the case. Isletl was shown to be highly expressed in the urogential sinus, suggesting that the differential expression between MM and IM was due to slight contamination of tissue caudal to the MM.

In Figure 2, it can be seen that several genes were clearly verified as being expressed within the MM itself, particularly ewing sarcoma homolog (ewsh),

tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, theta polypeptide (14-3-3 theta), retinoic acid receptor alpha (RAR<x) and stearoyl-coenzyme A desaturase 2 (Scd2). In explant cultures, 14-3-3 theta and Scd2 showed similar expression patterns being broadly expressed by epithelial segments, RARE was expressed in the renal interstitium, particularly the interstitium at the core of the explant, and ewsh was downregulated and expressed throughout the kidney. These markers may act as good RT-PCR probes to determine the renal potential of differentiating embryonic stem (ES) cell cultures.

In Figure 5, a similar WISH verification screen was performed on a subset of genes from the Compugen expreesion profiling. Here it can be particularly seen that Crym, Hoxal ls, CD83, Ogfr, Smoc2, Itm2c, albumin 1, Anapc7, somatostatin and IGF2bpl show differential expression in the E10. 5 MM to varying extents.

Of particular note was crystallin-mu (Crym) which showed a very specific expression profile. This gene was very highly and specifically expressed in the MM at E10. 5 and was localised to cap mesenchyme in metanephric explants. The specific spatiotemporal expression pattern of this gene makes it attractive candidate for the production of transgenic mice to isolate specific cell populations during kidney development that may retain inherent differentiation plasticity.

Also of interest was the secreted molecule Smco2 which was highly specific to the UB and MM at E10. 5 and was upregulated in ureteric bud tips in metanephric explants. Other highly verified genes included Ogfr, CD81, CD83, Nrpl, Hoxal Is and Gdnf, although not all are illustrated in the examples.

Cell Surface MarAsers of Renal Progenitor Cells Within the data from both expression profiling platforms, a subset of predicted transmembrane proteins were identified which showed a significant increase in expression in the E10. 5 MM compared to the surrounding IM (Table 4). Although predicted as transmembrane, Scd2 is known to be an intracellular transmembrane protein localised to the endoplasmic reticulum and was not considered as a potential cell surface marker of renal progenitors. The in situ expression patterns of some of these genes were examined in E10. 5 embryo

wholemounts to observe expression at the renal progenitor timepoint, E12. 5 urogenital tracts to determine specificity to the renal population and metanephric explants and E15. 5 kidney sections to resolve what renal cell types expressed these markers as development progressed (Figure 3 and 5 (Ogfr and CD83)).

This also allowed the identification of genes that were outliers because of expression in the ND. These included claudin-6 and spint-2. Expression of these two genes was very specific to the ND and primordial UB in the E10. 5 embryo and to ND/UB derivatives in the E12. 5 UG tract (spint-2 also showed strong expression in the gonads at E12.5) and metanephric explants. Expression was also observed in the mesonephroi at E12. 5.

Although present in other areas of the embryo, expression of CD24a antigen was strikingly specific to the uninduced MM population in the mesoderm of the E10.5 embryo (Figure 3). CD24a was expressed only in the MM and not throughout the nephrogenic cord. CD24a was specifically expressed in the kidneys of the E12.5 UG tract although weak expression was also observed in the ND at this timepoint, made difficult to see due to the strong expression in the kidneys. In the explant, CD24a was expressed in epithelial cells of both UB and MM lineages, although not in the lower limbs of the S-shaped bodies that give rise to the glomeruli. Cadherin-11 showed expression in the mesoderm at E10. 5, but particularly the renal progenitor population. Expression of cadherin-11 became more widespread at E12.5 but was strongly expressed throughout the renal interstitium of the explant, particularly the cells surrounding the UB tips.

The full-length transcript representing the EST BG072301 encodes for a protein for which little infonnation is currently known. There was apparently ubiquitous expression of this molecule across the embryo at E10.5 and E12.5, although the levels of expression were elevated in the E10. 5 MM. In explants and sections, expression was observed in the interstitium but particularly the mesenchymal cells bordering epithelial structures.

Using Known Stem Cell Markers to Identify Renal Progenitors As the renal progenitor population may represent potential stem cells, the expression of seven known markers of multipotential and pluripotential stem cell populations in the uninduced MM were analysed (Figure 4). While all of these

stem cell markers were represented in the NIA gene set (Table 7), the signal strength was low resulting in B-scores <0 for all but Oct-4, podocalyxin-like (podxl) and nestin. All three of these genes were more strongly expressed in the IM than the MM.

The transcription factors Oct-4 and nanog are markers of the pluripotential state. At E10. 5, expression of Oct-4 was restricted to primordial germ cells migrating through the urogenital ridge while nanog expression was observed in a non-specific fashion throughout the embryo, although seemingly higher in the E10. 5 MM. Neither of these genes showed any expression in metanephric explants. These stem cell markers would be unlikely to be of use according to the present invention The somatic stem cell markers CD34, podxl and nestin did not appear to mark the renal progenitor population. CD34 was expressed throughout the forming vasculature of the embryo and metanephric explant, but no expression was detected in E10. 5 MM. The recently identified haemangioblast marker podxl was expressed strongly in the aorta-gonad-mesonephros region at E10. 5, but not in the uninduced MM. In explants, expression of podxl was restricted to presumptive podocytes. The neural progenitor marker nestin was strongly expressed in the ectoderm of the E10. 5 embryo but not in the MM, although expression of nestin was observed in the S-shaped bodies of metanephric explants. A lack of expression of CD34 would be of value to determine a lack of heamatopoietic origin.

Of the stem cell markers surveyed in this report, the receptor tyrosine kinase c-kit (CD117) and the surface glycoprotein stem cell antigen-1 (sca-1) showed the most potential to act as markers of renal progenitors. At E10. 5, both sca-1 and c-kit were expressed throughout the nephrogenic cord with sca-1 in particular showing an increase in expression in the E10. 5 MM. In metanephric explants, sca-1 was expressed by the primitive nephron tubules of the while c-kit expression was observed throughout the primary renal interstitium. Hence, renal progenitors would show a phenotype that was Oct-4-, nanogl°/~, nesting, Sca, c- kit, CD34-.

EXAMPLE 2

Molecular Markers of Renal Cells Methods and Materials Fluorescent-Activated Cell Sorting 6-8 week old outbred CD1 mice were culled by cervical dislocation (Animal ethics committee approval number IMB/479/02/NIH) for harvest of kidneys and bone marrow. Adults kidneys were harvested into cold HANKS balanced salt solution (Sigma) and trimmed of all excess connective tissue.

Femurs and tibias were flushed with cold PBS + 2% FCS using a 27 gauge needle to collect bone marrow. For embryonic kidney tissue collection, naturally mated outbred CD1 females were sacrificed as above at E15.5 and E10. 5. Kidneys were dissected from embryos in cold L15 media (Gibco).

Tissue was minced into a coarse slurry with scissors and digested in 10 mg/mL collagenase B (Roche), 1.2 U/mL dispase II (Roche), 0. 01% DNase type I (Sigma) in HANKS for 20 minutes at 37°C with agitation. The concentration of collagenase was reduced to 1 mg/mL for dissociation of embryonic tissue.

Digested tissue was dissociated further using 23 gauge needles before being passed through a 40 JM cell strainer (BD Falcon). Red blood cells were lysed using Gey's solution and cells were resuspended in pre-warmed DMEM-phenol red (Gibco), 10 mM HEPES, 2% FCS at a concentration of 1 x 106/mL. For hoechst staining, 5 zg/mL hoechst 33342 (Sigma) was added to each sample and incubated at 37°C for 90 minutes under protection from light. A control tube for each sample containing 50 ; je verapamil (Sigma) was included in each preparation to set the side population gate. After hoechst staining, cells were washed in PBS + 2% FCS and subsequently stained with fluorescein isothiocyanate (FITC) and phycoerythrin (PE) conjugated antibodies for 20 minutes on ice. The following directly conjugated anti-mouse monoclonal antibodies were used-CD45-FITC (clone 30-F11), CD31-PE (clone MEC13. 3), sca-l-PE (clone E13-161.7), c-kit-FITC (clone 2B8) and CD24a-PE (clone Ml/69) (Pharmingen). Non-conjugated CD34 (Zymed), CD24a (Pharmingen) and cadherin-11 (Santa Cruz) primary antibodies were also used which were then subsequently stained with anti-mouse-FITC, anti-rat-FITC and anti-goat-PE

secondary antibodies (Sigma) respectively. Finally, 2 llg/mL 7- aminoactinomycin D (7-AAD, Sigma) was added to each sample to identify viable cells.

Cells were analysed and sorted on a FACS Vantage SE (Becton Dickinson) with both 488 nm argon (200 mW power) and 365 nm ultra-violet (50 mW power) lasers. FITC and PE were excited with the 488 nm laser and emission signals were detected using 530/30 and 575/25 band pass filters respectively. Hoechst and 7-AAD were excited with the 365 nm laser and emission detected using a 670/40 filter for 7-AAD and 424/44 (blue) and 660/20 (red) filters for hoechst. Compensation was adjusted using samples stained with one fluorochrome only and the side population gate was set using verapamil control samples. Data were acquired using CellQuest software (Becton Dickinson) and analysed with winMDI 2.8.

Results One of the major goals of this screen was to identify cell surface markers that may be used to isolate potential renal stem cells based on their similarity to E10. 5 MM. From the NIA microarray analysis, two cell surface molecules displayed expression patterns that make them attractive candidates for this purpose-CD24a and cadherin-11. From the Compugen array analysis, a further 45 cell surface markers of interest were identified which are indicated in Table 3 as non-intracellular C, D and E class genes, with the exception of Spint-2 and claudin 6. Additionally, analysis using NIA chips identified Spint-2 and claudin 6 as good markers for progenitors of the collecting tubules of the kidney, based on their expression in the ureteric bud of the E10. 5 metanephros.

Focussing on CD24a and cadherin-11, we have further sought to validate their utility for the identification and isolation of renal progenitors and potentially also the identification and isolation or adult renal stem cells. Referring to Figure.

6, both of these genes were strongly and specifically expressed in the E10. 5 MM although in later metanephric development CD24a is located in all epithelial structures while cadherin-11 is expressed in the primary interstitium. However, both overlap clearly in the cap mesenchyme from E10.5 to around E15.5. Cap

mesenchyme is derived from metanephric mesenhyme and surrounds the tips of the advancing ureteric buds, giving rise to all elements of the developing nephrons. Section in situ analysis was conducted to resolve what cell types expressed these genes throughout subsequent stages of kidney development.

Cells co-expressing these molecules in the adult kidney may possess a phenotype more similar to that of the renal progenitor population and retain a degree of inherent differentiation capacity. In E13. 5 and E15. 5 kidney sections, CD24a and cadherin-11 expression remains in the structures observed in metanephric explants, namely epithelial nephron segments and the interstitium respectively. In the adult kidney, CD24a is expressed principally in distal convoluted tubules while cadherin-11 expression is also seen in distal tubules and loop of Henle segments. No expression of cadherin-11 is seen in any interstitial cell population in the adult.

Immunophenotyping was done by FACS analysis to determine the proportion of renal cells, if any, which retained expression of both CD24a and cadherin-11 during development (FIG. 7). Three timepoints were analysed, the E10. 5 MM, E15. 5 metanephroi and adult kidneys. As anticipated, the proportion of CD24a+cad-11+ cells in the kidney decreased throughout development, dropping from 16. 22% of the total cell population at E10. 5 to 8.13% at E15.5 to 4.39% in the adult. Specific markers of renal progenitor cells that continue to be expressed in a stem cell population should decrease in abundance as the kidney develops and differentiates and the progenitor pool becomes depleted.

Of interest with regard to CD24a marking a potential stem cell population in the kidney, this molecule was shown to be strongly expressed by kidney side population cells. Side population cells are a specific subpopulation of cells isolated by FACS on the basis of their ability to rapidly efflux the vital dye Hoechst 33342 that have been shown to be highly enriched for stem cells from a number of organs (Goodell MA. Multipotential stem cells and'side population' cells. Cytotherapy. 2002; 4 (6): 507-8). The SP represent approximately 0.1-0. 2% of the total cell population from E15.5 and adult kidneys and approximately 91% and 67% of these embryonic and adult kidney SP cells respectively express CD24a when overlayed on isotype matched controls (FIG. 8). The observation

that CD24a has been identified as a potential renal stem cell marker by two independent experiments (microarray analysis at the renal progenitor timepoint, FACS analysis of kidney side population cells) enhances the likelihood that this molecule may mark a renal stem cell population.

Discussion Of the genes identified as enriched in the uninduced MM from microarray analysis, CD24a antigen and cadherin-11 appear to be the best candidates for renal progenitor cell surface markers. CD24a was strongly and specifically expressed in all uninduced MM cells at E10. 5 while cadherin-11 is also strongly expressed by this population. Although these molecules both appear to mark the renal progenitor population, their expression patterns diverged greatly as kidney development progressed. In metanephric explants, CD24a expression was observed in all epithelial structures of the developing kidney except for the lower limbs of the S-shaped bodies while cadherin-11 was expressed by mesenchymal cells of the renal interstitium, most strongly by those surrounding the UB tips, but not in epithelial cells. The fact that CD24a marks cell types of both MM and UB derivatives suggests that it identifies renal progenitors committed to differentiating into epithelial segments of the nephron while cadherin-11 may identify MM cells destined to form the renal interstitium. If individual cells of the uninduced MM co-expressed CD24a and cadherin-11, they may represent a renal stem cell population that has the ability to form all differentiated cell types found in the mature organ.

There is some indirect evidence to suggest that CD24a may mark a renal stem cell population. The human ortholog, CD24, is strongly expressed in Wilms' tumours (Droz et al., 190, Hum. Pathol. 21 536-544) and renal cell carcinomas (Droz et al., 1990, Am. J. Pathol. 137 895-905). Expression of human CD24 by renal tumour cells may indicate these cells are reverting to a more primitive or embryonic state, a condition analogous to the undifferentiated MM at E10. 5.

CD24a/CD24 may represent a marker of renal progenitor cells conserved between murine and human systems but its expression is not restricted to the uninduced MM and it will be necessary to use other markers in combination with CD24a to specifically purify renal progenitors. CD24a+ was successfully used to

isolate cells from murine embryonic and adult kidneys by FACS, demonstrating the utility of the cell surface markers in this invention.

Several other markers within the high priority list provided, including CD83, CD81 and CD164, have associations with haematopoietic progenitors.

CD83 is a marker of dendritic cells (Lechmann et al., 2002, Trends Immunol.

2002, 23 273-5). CD164 and CD81 are enriched in a population of bone marrow derived cells with multi-lineage potential (MIAMI cells) (D'Ippolito et al., 2004, J. Cell Sci. 117 2971-81).

While claudin-6 and spint-2 showed tremendous specificity of expression in the ND and UB, the UB has a much smaller differentiation spectrum than the MM and is not likely to be the source of a stem cell population. However, the existence of a single nephrogenic progenitor is not clear because it is uncertain whether all epithelial cell types in the adult kidney can be derived from a single precursor cell or whether each cell type has its own precursors (A1 Awqati & Oliver, 2002, supra). Therefore, cellular therapy of kidney diseases may require isolation of two distinct progenitor populations, one from the MM and one from the UB, in which case these markers would prove useful.

The distinct expression of common stem cell markers in the uninduced MM at E10. 5 was not detected by microarray analysis or in situ hybridisation.

The pluripotency markers Oct-4 and nanog were not observed in the uninduced MM or metanpehric explants which is as expected from a progenitor population restricted to mesodermal differentiation. Of the somatic stem cell markers surveyed, c-kit and sca-1 were expressed in the E10. 5 MM but also throughout the nephrogenic cord, the tissue that gives rise to all three mammalian excretory entities. These cell surface proteins have traditionally been used to identify various lineages of bone-marrow derived stem cells (Ma et al., 2002, Br. J.

Haematol. 116 401-408; Meirelles et al., 2003, Br. J. Haematol. 123 702- 711) ;, but more recently have also been used to isolate stem cells from other organs such as muscle (Howell et al., 2003, Ann. NY Acad. Sci. 996 158-173) testis (Kubota et al., 2003, Proc. Natl. Acad. Sci. USA 100 6487-6492) and mammary gland (Welm et al., 2002,245 42-56). In metanephric explants, sca-1

was expressed by the primitive tubules of the nephrons. Recent studies with BrdU and label-retaining cells in the kidneys have demonstrated slow-cycling cells able to respond to kidney damage by proliferation located in these tubular structures in mature kidneys (Maeshima et al., 2003, J. Am. Scoc. Nephrol. 14 3138-3146), demonstrating the possible persistence of progenitor-like cells in this niche. C-kit expression was observed throughout the primary renal interstitium of the explant which is also of interest as certain interstitial cells of the adult kidney have been suggested to possess the ability to undergo a mesenchymal-epithelial transdifferentiation to replace injured tubular cells (Nadasdy et al., 1994, Hum Pathol. 25 22-28).

Gene knockout models have implied crucial roles for molecules such as WT-1 (Kreidberg et al., 1993, Cell, supra), Liml (Fujii et al., 1994, Dev. Dyn. supra), Eyal (Stuart et al., 2003, supra) and Pax2 (Torres et al., 1995, supra) in early metanephric development. Expression of these genes are thought to be some of the earliest signs of commitment of the metanephric mesenchyme to a renal fate. Many of these genes were not represented in the NIA clone set and some genes that were present did not produce a signal strength that would allow a reliable determination of differential expression to be made, resulting in a B-score <0. However, two genes involved in early metanephric development, the transcription factor WT-1 and the secreted morphogen wnt-4, showed higher expression in the IM compared to the MM in microarrays (fold change just below 1. 80-fold threshold), findings confirmed by in situ hybridisation (results not shown). This highlights the fact that a comparison between IM and MM at E10. 5 essentially represents a spatial comparison between mesonephros/presumptive genital ridge and MM. Hence, some genes that play important roles in metanephric development will initially be expressed to a higher degree in the mesonephros/genital ridge than the MM.

In summary, for the first time we have catalogued the expression profile of the MM at the point of commitment to a metanephric lineage. Using both the NIA cDNA and Compugen long oligonucleotide clone sets, this analysis has identified markers (Tables 2 and 3) as molecules highly expressed by renal progenitors which could be used as a set of markers for renal progenitor

identification and isolation. A high priority subset of these markers, shown in Table 4 have been verified to display enriched expression in the region of the E10. 5 murine MM. This high priority list includes8 cell surface markers including those genes in Table 4 with a predicted membanre organization of Class C, D or E (excluding those known to reside on within an intracellular membrane). These 49 cell surface markers, comprising (all C, D and E genes in Table 4 other than Spint- 2, claudin 6 and the 2 or 3 marked as intracellular), could be used to isolate, enrich or purify renal progenitors at this timepoint or from stem cells induced to adopt a renal progenitor phenotype in vivo or in culture. Spint2 and claudin 6 mark the primitive ureteric bud rather than the MM and would therefore be useful in the isolation of prospective progenitors of the renal collecting ducts.

By distinguishing some of the earliest genes expressed by the uninduced MM, this invention has not only identified novel molecules involved in metanephric development, but provided tools for the RT-PCR-based identification of ES cells adopting a renal fate. While the existence of an adult renal stem cell has not been established, recent discoveries in stem cell biology suggest that they might exist, although no markers for renal stem or progenitor cells had been discovered, prohibiting the identification and isolation of such cells. By defining a combination of cell surface proteins that specifically mark the renal progenitor population, this invention will facilitate purification of cells with this phenotype from mixed populations, such as kidneys at various stages of development or differentiating ES cell cultures, using antibody-based FACS.

An isolation protocol based upon these renal progenitor/metanephric mesenchyme enriched cell surface proteins, together with the information on known stem cell markers that lie on the cell surface, renal progenitors would preferably show a phenotype that was CD24a+, cadherin ll+c-kit +/I°WSca-l+/l°w CD34- It will be appreciated by the skilled person that the present invention is not limited to the embodiments described in detail herein, and that a variety of other embodiments may be contemplated which are nevertheless consistent with the broad spirit and scope of the invention.

Table 1

Class Description Spb TMDE A Soluble, intracellular protein No No Soluble, secreted protein Yes No C Type I membrane protein Yes Yes D Type II membrane protein No Yes E Multi-span membrane protein Yes or No >1 F Unclassified: conflicting predictions ? ? a Membrane organization class b Presence of a signal peptide c Presence of a transmembrane domain Table 2 Fold Membrane Probe ID Change Common Description Localisation RefSeq UniGene B-stat IMBCCOOla04 3. 64 Heat shock protein, 60 kDa (Hspdl) F NM 010477 Mm. 299398 5. 733 BG082455 3. 12 Cfdn6 claudin 6 E NM 018777 Mm. 86421 5. 101 BG071497 2. 52 Ewsh Ewing sarcoma homolog _ A NM_007968 Mm. 142822 5. 921 BG073496 2. 42 RdhlO retinol dehydroRenase 10 (at)-trans) 0NM133832 Mm. 274376 2. 453 IMBCCOOICOS 2. 39 _ Cadherin 11 C NM 009866 Mm. 1571 1. 054 BG085134 2. 3S Cd24a CD24a antioen C NM_009846 Mm. 29742 3. 247 IMBCCOOldl3 2. 32 53 Transformation related protein 53 (PS3) A NM_011640 Mm. 222 1. 714 IMBCC002doI 2. 25 GATA3 GATA binding Proteln 3 Gata3 A NM 00809I Mm. 289671 6. 921 tyrosine 3-monooxygenase/tryptophan 5- monooxygenase activation protein, theta BG084914 2. 23 Ywhaq polypeptide A _ NM_011739 Mm. 289630 2. 366 BG071792 2. 16 1110Q34A24Rlk RIKEN cDNA I1iO034A24 oeneFNM027269 Mm. 107180 2. 400 IMBCCOOldlS 2. 10 RARa Retinoicacid receptor alpha (RARa A NM 009024 Mm. 103336 1. 346 BG085206 2. 06 Spint2 serineprotease ! nhlbitor, Kunitz type 2 _ _ C NM_011464 Mm. 295230 5. 178 IMBCC001c22 2. 06 H19 H19 foetal liver mRNA (HI9 F X58196 Mm. 14802 5. 144 BG072301 2. 04 Mus musculus transcribed sequences E BG085135 Mm. 195726 4. 448 Bone morphogenetic protein 7 (BMP7) ; osteogenic IMBCC002 03 2, 02 BMP7prptetn 1BNM007557 Mm. 595 0. 164 BG066641 2. 00 Scd2-stear I-Coen me A desaturase 2ENM009128 Mm. 193096 3. 244 BG073524 1. 9t Spint2_ serine protease Inhibitor, Kunitz type 2 _ C NM_011464 Mm. 295230 4. 390 BG076069 1. 88 Cd24aCD24a antfgenCNMOQ9846 Mm. 29742 4. 260 solute carrler family 2 (facilitated glucose BG064126 1. 84 Sfc2altransporter), member 1ENM011400 Mm. 21002 2. 356 BG077268 1. 84 Tcpl t-complex protein 1 A NM_013686 Mm. 32019 5. 585 BGQ78410 1. 83 Enol_ enolase t, alPha non-neuron A NM_023119 Mm. 70666 2. 330 IMBCC002c07 1.82 H19 H19 foetal liver mRNA (H19) F X58196 Mm.14802 5.144 BG066514 1.82 2410129E14Rik RIKEN cDNA 2410129E14 gene A NM_023716 Mm.194735 2.748 BG086076 1.80 Rsdr1-pending retinal short-chain dehydrogenase/reductase 1 B NM_011303 Mm.14063 1.292 AW548498 1.80 Unknown EST A 2.950 Table 3 Fold Membrane Probe ID Change Common Description Localisation RefSe UniGene B-stat CGENMOUSE30012021 62. 41 Hoxdl3 Homeo box D13 F NM_008275 Mm. 57227 2. 615 CGENMOUSEEXT31125581 22. 69 Oqfr Oplold qrowth factor receptorANM031373 Mm. 250418 3. 224 CGEN_MOUSE_ExT=3200032_1 13. 74 Unknown EST no match U63760 1. 801 CGENMOUSEEXT31060861 13. 08 4930506L13Rik RIKEN cDNA 4930506L13 gene E BC004773 Mm. 282339 0. 022 CGEN MOUSE EXT 3102946 1 11. 48 Dscamll Down syndrome cell adhesion molecule-like I A AK014832 Mm. 325499 0. 745 CGEN_MOUSE_EXT 3103277_1 10. 36 P2 5 Purinergic receptor Yamil A group 5) E AK011967 Mm. 320228 4. 341 CGEN MOUSE EXT 3112831_1 9. 57 Gfm G elongat (on factor F BC013093 Mm. 122466 0. 177 CGEN_MOUSE EXT_3101313_1 9. 46 Unknown EST 0 AF056216 0. 830 CGEN_MOUSE_3001434_1 7. 99 SIX2 Sine oculis-related homeobox 2 homolog (Drosophlla) A D83147 Mm. 5039 0. 184 CGEN_MOUSE_3006486 1 7. 47 HoxalO Homeo box A10ANM008263 Mm. 56. 764 CGENMOUSEEXT31057071 7. 41 Z 335 Zinc fln 2r rotein 335 0 AK007785 Mm330776 7. 423 CGEN MOUSE 3005338 1 6. 75 Sdcb Svndecan bindln rotein D NM 016807 Mm. 247473 5. 144 CGEN_MOUSE_ExT 3103663_1 6. 69 1700013H16R (k RIKEN cDNA 1700013H16 gene A AK005953 Mm. 116929 0. 972 CGEN MOUSE 3002179 1 6. 51 Npe s Aminopeptidase puromycin sensitive B NM 008942 Mm. 29824 3. 670 CGEN MOUSE30005421 6. 49 Cyflpl Cytoplasmic FM R11nteractlng proteln 1 A N M_011370 Mm*37249 4. 060 CGEN_MOUSE_EXT_3110531_1 6. 15 Pygo2 Pygopus 2 no rot AK004486 Mm. 22521 0. 999 CGEN MOUSE 3005356 1 6. 14 Cdl64 CD164 antigen C NM 016898 Mm. 269815 0. 290 CGEN MOUSE 3006543 1 6. 06 Itm2c Integral membrane protein 2C D AB030199 Mm. 29870 4. 298 CGEN MOUSE EXT_3114181_1 6. 01 Tars Threonyl-tRNA synthebse A _ NM_033074 Mm. 286061 5. 269 CGEN MOUSE_3003427_1 5. 93 Kpna2 Karvopherln (Importin) alpha 2 _ A NM_010655 Mm. 12508 6. 330 CGEN MOUSE 3006079_1 5. 89 G3b Ras-GTPase-activating protein SH3-domain binding protein A NM_013716 Mm. 39631 4. 648 CGENMOUSEEXT31128241 5. 88 Prkcl Proteln kinase C"ota no_prot AK009442 Mm. 291554 4. 041 CGEN_MOUSE_3001627_1 5. 88 Hnrpu Heterogeneous nuclear ribonucleoproteln U A NM_016805 Mm. 2115 6. 783 CGEN_MOUSE_3002684_1 5. 81 Mcm7 Mlnichromosome maintenance deficient 7 (S. cerevisiae) A NM_008568 Mm. 241714 7. 547 CGEN_MOUSE_EXT_3108113_i 5. 76 2610312E17Rik RIKEN cDNA 2610312E17 gene _ A BC005755 Mm. 5110 6. 477 CGEN MOUSE 3006165 1 5. 76 Vamp3 Vesicle-associated membrane protein 3 D NM 009498 Mm. 273930 2. 738 CGEN_MOUSE 3001513_1 5. 67 Zf422 Zinc flnger protein 422 A AF281634 Mm. 18810 0. 391 CGEN MOUSE EXT_310826o 1 5. 64 Eif3s9 Eukaryotic translation (nitiation factor 3, subunit 9 (eta) A SC007175 Mm. 2167i 0. 082 CGEN_MOUSE_3002623_1 5. 63 Acat2 Acetyl-Coenzyme A acetyltransferase 2 A M35797 Mm. 229342 2. 624 CGEN MOUSE EXT_3104480_1 5. 55 Slc35f5 Solute carrierfamily 35, member FS E AK004892 Mm. 28654 6. 177 CGEN_MOUSE_ExT_3104363_1 5. 50 Dars Aspari-yl-tRNA synthetase A BC008638 Mm. 28693 4. 822 CGEN MOUSE 3000939 1 5. 44 Hoxalls Homeo box All, opposite strand transcript no rot U20366 Mm. 360304 3. 774 CGEN MOUSE EXT_3106870_1 5. 41 Sall4 Sal-like 4 (Drosophila) no_match AF285588 Mm. 256916 2. 520 CGEN_MOUSE_EXT_3108374_1 5. 41 Unknown EST 0 S68108 3. 611 CGEN MOUSE 3005056 1 5. 33 Gjal Gap junction membrane channel protein alpha i E NM_010288 Mm. 370184 2. 612 CGEN MOUSE_3004058_ 5. 32 Actr3 ARP3 actin-retated protein 3 homolog (yeast) A AF307855 Mm. 183102 5. 407 CGEN MOUSE 3003425 1 5. 16 KPnbi Karyopherln (Importin) beta 1 A NM 008379 Mm. 251013 5. 603 Par-6 partitioning defective 6 homolog gamma (C. CGEN MOUSE_3004480_1 5. 14 Pard6g elegans A AF252290 Mm. 24678 0. 369 CGEN MOUSE 3004845 1 5. 13 Lmnbl Lamin 81 A NM 010721 Mm. 4105 4. 310 CGENMOUSE30057251 5. 08 Sdfri Stromal cell derived factor receptor 1CNM009145 Mm. 15125 1. 548 CGENMOUSE30024161 5. 08 Aral Arginase 1 liver A NM 007482 Mm. 154144 7. 061 CGENMOUSE30062681 5. 06 Zik1 Zinc flnger protein Interactin with K protein 1 A NM 009577 Mm. 49441 2. 472 CGEN_MOUSE_3003407_1 5. 06 Copb2 Coatomer protein complex, subunit beta 2 (beta rime A AF043120 Mm. 261735 4. 987 CGENMOUSE30046231 4. 90 Cdc451 Cell division cycle 45 homolog (S. cerevlsiae)-like A NM_009862 Mm. 1248 2. 136 CGEN_MOUSE_3006084_1 4. 87 Tdel Tumor dlfferentlally expressed 1 E NM_012032 Mm. 218473 3. 426 CGEN MOUSE EXT 3111172 1 4. 86 i 110004P21 Rlk RIKEN cDNA 1110004P21 gene A AK018483 Mm. 257276 4. 071 CGENMOUSE30039531 4. 83 Hspa8Heat shock protefn 8 A M19141 Mm. 336743 6. 115 CGENMOUSE30054821 4. 75 Capn6 Calpain 6 A NM 007603 Mm. 30290 0. 572 CGENMOUSEEXT31002081 4. 71 Antxr2RIKEN eDNA C430019N01 gene0 BC003908 Mm. 240351 0. 572 CGEN_MOUSE_3007381_l 4. 70 9130413I22R ! k RIKEN cDNA 9130413122 gene A AB041651 Mm. 332336 2. 622 CGENMOUSE 30017901 4. 70 Eef2 Eukaryotic translation elongation factor 2 A U89416 Mm. 289431 5. 385 CGEN_MOUSE 3005975_1 4. 65Unknown EST ANM0096283. 442 CGEN MOUSE 3006059_1 4. 62 Tebp Telomerase binding proteln, p23 A AF153479 Mm. 305816 5. 232 CGEN_MOUSE 3003131_1 4. 58 Slc30a9 Solute carrier family 30 (zinc transporter), member 9 no match AF263460 Mm. 234455 1. 885 CGEN_MOUSE 3003609_1 4. 57 Stipl Stress-lnduced phosphoproteln 1 A U27830 Mm. 258633 1. 982 CGENMOUSE 30027641 4. 54 CYP51 Cytochrome P450, familY 51 D NM_020010 Mm. 140158 4. 217 CGEN_MOUSE_EXT_3110074_1 4. 49 Chcll Chromosome condensation 1-like A BC003224 Mm. 280068 5. 344 CGEN_MOUSE_EXT_3108144_1 4. 46 Thumpdl THUMP domain containing1 A BC004776 Mm. 26392 2. 105 CGENMOUSEEXT31121391 4. 45 Fbxw11 RIKEN cDNAC530030P08 gene A AY038079 Mm. 28017 2. 066 CGEN_MOUSE_3000942_1 4. 37 Evxl Even sklpped homeotic aene i homoloq A Nom007966 Mm. 4910 0. 560 CGEN_MOUSE_EXT_3109449_1 4. 37 1810037K07Rlk RIKEN cDNA 4930565M07 gene ANM025962 Mm. 252785 3. 411 CGEN MOUSE 3005556 1 4. 35 Dscrl Down syndrome critical regfon homolog 1 (human) A NM019466 Mm. 265744 1. 504 CGEN MOUSE EXT 3109547 1 4. 30 Golph2 Golql phosphoprotein 2 no_prot BCOill52 Mm. 171335 2. 216 CGEN_MOUSE_3006777 1 4. 29 Cldn6 Claudin 6 ENM018777 Mm. 86421 0. 179 CGEN MOUSE EXT 3109107 1 4. 28 H2afy2 H2A histone famil member Y2 A NM 026230 Mm. 358707 5. 559 CGEN-MOUSE 006643_1 4. 28 Crym Crystaliln, mu A NM_016669 Mm. 9114 2. 583 CGEN_MOUSE_3005976 1 4. 26 Sst SomatosStin B NM_009215 Mm. 2453 1. 182 CGEN MOUSE 3004389 1 4. 25 Llglh Lethal cillant larvae homolog A _ NM_008502 Mm. 285453 1. 095 CGEN_MOUSE_EXT_3103694 1 4. 23 Unknown EST F AK011165 5. 621 CGEN MOUSE 3001229 1 4. 22 Hdaci Histone deacetylase I A NM 008228 Mm. 202504 2. 708 CGEN_MOUSE_EXT_3109129_1 4. 22 Prpl9 PRP19/PS04 homolog (S. cerevislae) A BC004070 Mm. 358657 6. 001 CGEN_MOUSE_EXT_3104662_1 4. 20 C330018J07Rik RIKEN cDNA C330018J07 gene no rot BC008232 Mm. 212606 4. 807 CGENMOUSE 30035251 4. 17 Calbl Calbindin-28K A NM 009788 Mm. 277665 2. 811 CGEN_MOUSE 3001597 1 4. 16 Sh3bgrl SH3-blnding domaln glubmic acid-rich proteln like A NM 019989 Mm. 260760 2. 289 CGEN MOUSE EXT 3106236 1 4. 12 BC002199 CDNA sequence BC002199 A BC002199 Mm. 215471 4. 417 CGEN_MOUSE 3004593_1 4. 10 Ier2 Immedlate earlY resPonse 2 A NM_010499 Mm. 399 3. 737 CGEN_MOUSE_EXT_3111314_1 4. 08 Rlan RNA Imprlnted and accumulated In nucleus no_rot AB063319 Mm. 293263 6. 522 CGEN_MOUSE EXT_3106592 1 4. 08 Gtpbp4 GTP binding proteln 4 A NM_027000 Mm. 41800 4. 456 CGEN_MOUSE., 3104863 1 4. 07 Golph3 Golgf hosphoprotein 3 A NM 025673 Mm. 250936 0. 321 CGEN_MOUSE_3004851_1 4. 05 Weel Wee 1 homolog (S. pombe) A NM_009516 Mm. 287173 1. 972 CGEN_MOUSE 3002045 1 4. 04 Ppp4c Protein phosphatase 4, catalytic subunit A NM_019674 Mm. 41998 4. 329 CGEN MOUSE EXT 3106496 1 4. 02 Slc39a7 Solute carrlerfamil 39 (zinctransporter member7 E NM 008202 Mm. 18556 3. 402 Protease (prosome, macropain) 26S subunit, non- CGEN_MOUSE 3002iL23_1 4. 02 Psmd2 ATPase, 2 A X80422 Mm. 243234 2. 039 CGEN_MOUSE_EXT_3104015 1 3. 96 Atadl ATPase family, AAA domain containing 1ANM026487 Mm. 27123 3. 804 CGEN MOUSE 3004314 1 3. 90 Kif22 Kinesin family member 22 A AF013119 Mm. 370289 3. 681 CGENMOUSE30033641 3. 90 Rabis RAS18, member RAS onco ene famil A NM 011225 Mm. 132802 0. 877 CGENMOUSE30041601 3. 87 Gmfb Glla maturatlon factor, beta A AF297220 Mm. 87312 3. 810 CGEN_MOUSE_EXT_3104362_1 3. 86 Rars Arginel-tRNA synthetase ~~-_ A AK011383 Mm. 284906 3. 627 CGENMOUSE300544613. 86 Cd83 CD83 antigenCNM009856 Mm. 57175 4. 852 CGEN MOUSE EXT 3113514 1 3. 86 AnkrdlO Ankyrln repeat domain 10 _ A BC002198 Mm. 12459 3. 776 CGENMOUSE30000601 3. 86 Maea MacroPhage erythroblast attacher A NM_021500 Mm. 281642 2. 095 CGEN_MOUSE EXT 3114168 1 3. 82 6530402N02Rlk RIKEN cDNA 6530402N02 gene no_prot BC012406 Mm. 337825 3. 411 CGENMOUSEE) n3105716l 3. 81 2810422M04Rik RIKEN cDNA 2810422M04gene A NM 025640 Mm. 87456 3. 950 Prote ! n phosphatase 1G (formerly 2C), magnesium- CGEN MOUSE 3004657_1 3. 79 Ppmi dependent, gamma isoform A NM 008014 Mm. 14501 1. 149 CGEN_MOUSE_3005773 1 3. 78 Gdnf Gilal cell llne derived neurotrophicfactor _ B NM_010275 Mm. 4679 2. 972 CGEN MOUSE EXT 3103406 1 3. 76 2610040E16Rlk RIKEN cDNA 2610040E16 gene A NM_024194 Mm. 358704 2. 391 CGENMOUSE30026001 3. 75 Stard7 START domain containing 7 0 AF244543 Mm. 41271 0. 329 CGEN MOUSE 3004737 1 3. 72 AI316802Expressed sequence AI316802FAF151110 Mm. 337784 2. 082 CGEN_MOUSE_3006671 1 3. 72 Frzb Frinled-related proteln B NM_011356 Mm. 314721 0. 237 CGEN_MOUSE_EXT_3106808 i 3. 71 Ccarl Cell divlsion cycle and apoptosis regulator 1 A AK012111 Mm. 196371 2. 423 CGEN_MOUSE 3006158 1 3. 70 S I S na to h sin-Iike rotein E NM 013635 Mm. 246304 4. 911 CGEN_MOUSE_EXT_3105736 1 3. 70 D5Ertd689e DNA segment, Chr 5, ERATO Dol 689, expressed 0 AK004410 Mm. 249474 2. 049 CGEN_MOUSE_EXT_3105613_1 3. 69 Zmyndl9 Zlnc finger, MYND domain containing 19 _ A NM_026021 Mm. 296106 4. 262 CGENMOUSE3005586l 3. 69 App Amylold beta (A4) precursor proteinCNM007471 Mm. 277585 1. 957 CGENMOUSEEXT31043751 3. 67 4930429D17Rlk RIKEN cDNA 4930429D17 ene no rot AK015233 Mm. 159262 2. 446 CGEN MOUSE_3004807_1 3. 66 Ahapc7Anaphase promoMng comptex subuntt 7ANM019805 Mm. 37341 0. 698 CGEN_MOUSE_3003658_1 3. 66 Tacstdl Tumor-assoclated calclum signal transducer 1CNM008532 Mm. 4259 > 5. 328 CGEN_MOUSE 3002341_1 3. 66 Lylai Lysophospholipase 1 F NM 008866 Mm. 299955 2. 539 CGEN MOUSE EXT 3104587 1 3. 64 Senp2 SUMO/sentrln speclflc protease 2 F N M_029457 Mm. 297431 2. 465 CGEN_MOUSE_EXT_3108042_1 3. 64 Unknown EST A S502133 4. 702 CGEN_MOUSE_3002953_t 3. 62 Afp Alpha fetoproteXn B N M_007423 Mm. 358570 0. 261 CGEN MOUSE EXT 3105036 1 3. 61 RdhlO dehydrogenase 10 (all-trans) 0 AK014244 Mm. 274376 5. 084 CGEN_MOUSE 3000458_1 3. 57 Impdh2 Inosine 5-phosphate dehYdrogenase 2 A NM_011830 Mm. 6065 4. 931 C6ENMOUSE 30066081 3. 55 Qk QuakingANM021881 Mm. 262294 4. 248 CGEN_MOUSE_3003611_1 3. 55 Son Son cell proXferation proteln A NM_019973 Mm. 46401 1. 657 CGEN MOUSE EXT 3103427 1 3. 54 Dusp6 Dual speciflcity phosphatase 6 A NM_026268 Mm. 1791 2. 174 CGEN MOUSE 3003468 1 3. 53 Copbl Coatomer protein complex, subunit beta 1 A AF231925 Mm. 277024 1. 516 CGEN_MOUSE_EXT_3106097_1 3. 53 9430077D24Rlk RIKEN cDNA 9430077D24 gene A AK020492 Mm. 265125 0. 045 CGEN_MOUSE_EXT_3110507_1 3. 51 Rnfill Rlng flnger 111 A AF330197 Mm. 29783 2. 904 GEN Cr3105545l 3. 48 Unknown EST 0 AF182407 3. 610 CGEN MOUSE 3004319 1 3. 48 MtaplbMtcrotubub-assodated prctetn 1 BANM008634 Mm. 4173 1. 056 KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein CGEN MOUSE_EXT 3106582_1 3. 48 Kdelrlretention receptor 1 E BC011370 Mm. 298433 5. 945 CGEN_MOUSE_EXT_3103433_1 3. 47 3110057012R ! k RIKENcDMA 3110057012 genenoprotAK010105 Mm. 32373 1. 547 Golgi associated, gamma adaptin ear containing, ARF CGEN MOUSE EXT_3108846_1 3. 46 Gga2 binding proteln 2 F AK004632 Mm. 29619 3. 465 CGEN_MOUSE_EXT_3iO6271_1 3. 46 Scfdl Secl famil domain containing1 A AK014070 Mm. 216511 3. 545 CGEN MOUSE 3007258 1 3. 38 I l5 Interferon alpha responsive gene A AJ251363 Mm. 351270 3. 109 CGEN_MOUSE_3004659_1 3. 37 P) Polo-"ke kinase 2 (Drosophila) A M96163 Mm. 380 1. 321 CGEN_MOUSE_3002626_1 3. 37 Asahl N-acyIsphingosine amtdohydrolase 1 B NM 019734 Mm. 22547 2. 883 CGEN MOUSE EXT 3108115_1 3. 35 1300006C19Rik RIKEN cDNA 1300006C19 gene E BC013054 Mm. 296158 0. 176 CGEN_MOUSE_EXT_3113717 1 3. 33 2210409M21Rlk RIKEN cDNA 2210409M21 gene A BC013617 Mm. 285783 6. 567 CGEN MOUSE EXT 3110204 1 3. 32 Robo2 Roundabout homolog 2 (DrosophHa) noprot AK011188 Mm. 171736 3. 225 CGENMOUSEEXT31110621 3. 31 Cdc issoclated 7 A AK011289 Mm. 270676 6. 998 CGENMOUSEEXT31095551 3. 30 2310037I24Rik RIKEN cDNA 2310037124 geneABC003301 Mm. 296240 5. 095 CGENMOUSEEXT31061241 3. 30 Glmn Glomulin, FKBP associated protein A BC003446 Mm. 41417 3. 233 CGEN MOUSE EXT 3105755 1 3. 30 Hcngp Transcriptional regulator protein A NM_020483 Mm. 267810 2. 362 CGEN MOUSE EXT_3112088 1 3. 30 1600002H07Rlk RIKEN cDNA 1600002H07 gene A AK005395 Mm. 23881 1. 085 CGEN MOUSE 3001607 1 3. 29 Hnrpa2b1 Heterogeneous nuclear ribonucleoprote (n A2/Bl A NM 016806 Mm. 155896 3. 093 CGEN_MOUSE_3000651_1 3. 28 Tsnax Translln-assoclated factor XANM016909 Mm. 5248 4. 744 CGEN MOUSE_EXT_3105058_1 3. 27 1200006019Rlk RIKEN cDNA 1200006019 geneDNM026164 Mm. 54126 1. 016 CGEN_MOUSE_EXT_3103454_1 3. 26 Rab5a RABSA, member RAS anco ene famSf A NM 025887 Mm. 329123 2. 961 CGEN_MOUSE_EXT_3114032_1 3. 26 Maprel Mtcrotubule-associated proteln, RP/EB famil member 1 noprotAK017457 Mm. 143877 0. 607 Protein phosphatase 2 (formerly 2A), regulatory subunit B CGEN_MOUSE_EXT_3103191_i 3. 24 Ppp2r2a PR 52), alpha isoform A AK010380 Mm. 273997 3. 568 E CGEN_MOUSE_ExT_3100376_1 3. 22 Elovl6 acids (yeast) E AB072039 Mm. 314113 1. 630 CGEN MOUSE EXT_3105904_1 3. 21 Fbpl Far upstream element (FUSE) binding protein 1 A BC014763 Mm. 278922 5. 842 CGEN_MOUSE EXT 3105350 1 3. 21 Cstfl Cleavage *lmulatlon factor, 3 pre-RNA, subunit 1 A NM^024í99 Mm. 26944 0. 813 CGEN_MOUSE_3003369_1 3. 21 Fign l1 Fldgetin-llke 1 A NM_021891 Mm. 236114 0. 245 CGEN_MOUSE_EXT_3105351_1 3. 20 Igf2bp3 Insulin-like growth factor2, binding protein 3 A NM_023670 Mm. 281018 3. 433 CGEMMOUSE30006451 3. 18Unknown ESTAX166703. 606 Solute carrier family 6 (neurotransmittertransporter, CGENMOUSE30033231 3. 18 Slc6a6 taurine), member 6 E NM 009320 Mm. 247352 3. 914 CGEN MOUSE EXT 3114161 1 3. 17 Kctd5 Potassium channel tetramerisation domain containing 5 A AKOli637 Mm. 28171 1. 184 CGEN_MOUSE_3002353_1 3. i7 Uspl4 Ubiqultin speclflc protease i4 A NM_021522 Mm. 329277 1. 901 CGEN_MOUSE_EXT_3108055_1 3. 17 Actr8 ARP8 actin-related protein 8 homolog (S. cerevislae) A NM_027493 Mm. 215110 2. 276 CGEN MOUSE 3001811 1 3. 15 Farsib Phenylaianine-tRNA synthetase-like, beta subunit A AF123263 Mm. 28922 2. 267 CGEN_MOUSE_EXT_3105577 1 3. 15 1300010F03Rlk RIKEN cDNA 1300010F03 gene B AK004956 Mm. 159651 4. 148 CGEN MOUSE EXT 3114517 1 3. 15 Grcc3f Gene r (ch ciuster, C3f ene E AY028317 Mm. 273915 2. 831 CGENMOUSE30016501 3. 14 SnrP70 U1 small nuclear rlbonucleoPrOteln polypeptide A 0 NM_009224 Mm. 216386 3. 831 CGEN_MOUSE_EXT_3109476 i 3. 14 4930541M15Rik RIKEN cDNA 4930541M i5 gene 0 AKoo5444 Mm. 144143 2. 546 CGEN MOUSE_EXT_3111443_i 3. 13 5730461K03Rik RIKEN cDNA 5730461K03 gene A BC013470 Mm. 35105 3. 097 CGEN-MOUSE EKr 3106833 1 3. 10 Tri 59 TriDartite motif-containing 59 D NM-025863 Mm. 176695 6. 529 CGEN_MOUSE EXT_3100271_i 3. 08 DOH4Sii4 DNA segment, human D4S114 A X70398 Mm. 128733 5. 867 CGENMOUSEEXT31099021 3. 07 1810060J02Rlk RIKEN çDNA i8i0060302 gene A NM_025911 Mm. 209774 0. 463 CGEN MOUSE EXT 3105366_1 3. 07 Hnrpk Heterogeneous nuclear rlbonucleoproteln K A NM U25279 Mm. 288451 4. 518 CGEN_MOUSE_EXT_3113853 1 3. 06 Rbml9 RNA binding motif protein 19 A AK004657 Mm. 41022 0. 141 CGEN_MOUSE_3007284_1 3. 05 633Q407GilRlk RIKEN cDNA 6330407G11 4ene A AB041594 Mm. 27903 2. 649 CGEN_MOUSE_3002662_1 3. 04 PnlWprpl Pancreatic llpase related proteln 1 B NM_018874 Mm. 10753 1. 478 CGEN_MOUSE_EXr_3113154 1 3. 04 5730454BOSRik RIKEN cDNA 5730454B08 gene noprot AK003350 Mm. 245357 6. 222 CGEN-MOUSE EXTI-3108147 1 3. 03 2810008M24Rik RIKEN cDNA 281Q008M24 gene no rot BC004049 Mm. 29464 4. 507 CGEN_MOUSE EXT_311118i_t 3. 02 Unknown EST EU16277 1. 229 CGEN MOUSE EXT 3105688 1 3. 02 1110018312Rlk RIKEN cDNA 1110018312 gene A AK003781 Mm. 271817 5. 730 CGEN MOUSE_EXT 3108227 1 3. 01 C77668 Expressed sequence C77668 F BC003209 Mm. 268564 1. 349 CGEN MOUSE 3002466 1 2. 98 PrPsl Phosphorlbosyl pYrophosphate sYnthetase 1 A NM_021463 Mm. 287178 2. 540 Cystine and histidine-rich domain (CHORD)-containing, CGEN_MOUSE EXT_3103174 1 2. 98 Chordcl zinc-btnding protein 1 ANM025844 Mm. 103534 0. 942 CGENMOUSEEXT31075051 2. 98 Unknown EST A AK003393 4. 990 CGENMOUSEEXT31112921 2. 96 Il2 Interleukin enhance binding factor 2 A NM 026374 Mm. 227258 5. 441 CGEN MOUSE EXT 3107928 1 2. 94 2810037C14Rlk RIKEN cDNA 2810037C14 rzene B NM_026034 Mm. 260782 4. 512 CGEN_MOUSE_EXr_3104439_1 2. 94 Mesdc2 Mesoderm developmentcandtate 2 B NM 023403 Mm. 117365 4. 274 CGEN MOUSE 3002992 1 2. 94 Slc20al Solute carrier family 20, member 1 E NM 015747 Mm. 272675 0. 568 CGEN_MOUSE_3004312_1 2. 93 Tubb5Tubutn, beta 5ANM011655 Mm. 273538 5. 573 CGEN_MOUSE_EXT 3106777_1 2. 92 2610028H07Rlk RIKEN cDNA 2610028H07 gene A BC006738 Mm. 335449 4. 562 Translocase of outer mitochondrlal membrane 70 homolog CGEN_MOUSE_EXT_3103928_1 2. 92 Tomm70a A east F AK012084 Mm. 213292 4. 414 CGEN_MOUSE_EXT_3106134_1 2. 91 Rnbp9 RAN binding protein 9 A NM_019930 Mm. 148781 4. 528 CGEN_MOUSE_3003220 1 2. 91 Unknown ESr _ B M23015 0. 243 CGEN_MOUsE_EXT_3103662_1 2. 91 1700040F15R ! k RIKEN cDNA 1700040F15 qene no_prot AK006653 Mm. 293024 1. 439 CGEN MOUSE EX'f 3113195 1 2. 89 Qars Gluta minyl-tRNA sYnthetase A AK004814 Mm. 272427 3. 527 Proteasome (prosome, macropain) 26S subunit, non- 2. 88 PsmdS ATPase 5 A AK005335 Mm. 270632 5. 324 GEN-MOUSE. 3001813-1 1 2. 88 Vars2 Valyl-tRNA synthetase 2 A N M_011690 Mm. 28420 2. 475 CGENMOUSEEXT31076341 2. 87 Cndp2RIKEN cDNA 2900046H12 geneANM023149 Mm. 296463. 662 CGENMOUSE30051091 2. 87 Maged2 Melanoma antigen, famDy D, 2 A A] 277114 Mm. 22575 1. 044 CGEN_MOUSE_3002334 1 2. 86 UsplO Ubiqultin specIflc protease 10 A NM_009462 Mm. 256910 3. 594 CGENMOUSE30005251 2. 86 To TopoWsomerase (DNA) I A NM_009408 Mm. 217233 5. 862 CGEN_MOUSE_EXT_3103378_1 2. 86 Depdcia DEP domafn contafning la A BC005799 Mm. 46681 0. 481 CGEN MOUSE EXT 3107252 1 2. 86 Eml4 RIKEN cDNA F830004D09 gene A AK019611 Mm. 295565 5. 422 CGENMOUSEE) Cr3105493l 2. 85 Nr4al Nuclear receptor subfamily 4, group A, member 1ANM010444 Mm. 119 3. 568 CGEN MOUSE EXT 3110354 1 2. 85 1110014JO1Rik RIKEN cDNA 1110014J01 gene A BC012523 Mm. 30056 2. 288 CGENMOUSEEXT31102171 2. 84 4921521311Rlk RIKEN cDNA 4921521ill gene A AK014939 Mm. 252421 4. 048 CGEN_MOUSE_EXT_3113682_1 2. 82 Grwdl Glutamate-rich WD repeat containing 1 0 BC008121 Mm. 274847 2. 853 CGEN_MOUSE_3004294_1 2. 82 Cenpe Centromere protein E 0 AB001426 Mm. 161470 3. 843 CGEN_MOUSE_EXT_3110485_1 2. 81 D12Ertd551e DNA segment, Chr 12, ERATO Do 551, expressed 0 AK014813 Mm. 273755 0. 970 CGEN_MOUSE_EXT_3105889_1 2. 80 Polr3c Polymerase RNA) III (DNA directed) polypeptide C A AK016716 Mm. 276043 0. 303 CGEN_MOUSE_3006998_1 2. 80 DlErtd396e DNA segment, Chr 1, ERATO Dol 396, expressed A NM021421 Mm. 289914 2. 541 CGEN_MOUSE_EXT_3110028_i 2. 79 Dhx30 DEAH (Asp-Glu-Ala-His) box polypeptide 30 A AB047557 mm. 276305 3. 635 CGEN_MOUSE_EXT_3110449_1 2. 77 2310065K24Rik RIKEN cDNA 2310065K24 gene A AK010053 Mm. 250425 2. 643 Ubiquitin-conjugating enzyme E2G 1 (UBC7 homolog, C. CGEN MOUSE_EXT_3106182 1 2. 76 Ube2 1 ele ans B NM 025985 Mm. 340315 3. 891 CGEN_MOUSE_3004754_1 2. 75 Ccne2 Cyciln E2 A NM_009830 Mm. 35867 1. 484 CGEN MOUSE 3000986 1 2. 75 P al Pra al RING-H2 motff contatnin A NM 008853 Mm. 8211 4. 138 CGEN MOUSE_3006083 1 2. 74 Tde2 Tumor dlfferentlally expressed 2 E NM_019760 Mm. 29344 1. 330 CGEN MOUSE_3003487_1 2. 74 Stx5a RIKEN cDNA B930096F20 geneD NM019829 Mm. 153061 0. 522 CGENMOUSEEXT31119291 2. 73 Kns2 Klnesin 2 _ A NM_008450 Mm. 278357 0. 601 CGEN MOUSE EXT 3110229 1 2. 73 Ptk7 PTK7 protein tYrosXne kXnase 7 C AK018379 Mm. 181833 3. 914 CGEN_MOUSE EXT_3109465_1 2. 72 3110001I20Rlk HYpothetical proteln C630011I23 __ A AK013949 Mm. 138091 0. 752 Small glutamine-rich tetratricopeptide repeat (TPR)- CGEN_MOUSE_EXT_31144B5_1 2. 72 5 a containtn al ha A BC003836 Mm. 30068 2. 324 CGENMOUSE30020241 2. 72 Rockl Rho-associated coiled-coll forminn kinase 1 A NM 009071 Mm. 6710 0. 723 CGEN MOUSE 3003242 1 2. 71 Moa 1 Modulator of apoptosis 1 A AF305551 Mm. 291222 1. 532 CGEN MOUSE 3002783 1 2. 71 Nsdhl NAD P de endent stero (d deh dro enase-like D NM 010941 Mm. 38792 4. 068 CGEN MOUSE 3002088 1 2. 69 Ublela Ubiquitin-llke 1 (sentrin activating enzyme ElA A NM 019748 Mm. 258530 0. 082 CGEN_MOUSE_3001664_1 2. 69 No) Nucleolar protein 5 A NM_018868 Mm. 220367 4. 276 CGEN_MOUSE_3007521_1 2. 68 Kdelcl KDEi (LYs-Asp-Giu-Leu) contalninq 1 B A] 404004 Mm. 281714 1. 886 DNA segment, Chr 11, Bu (ogham & Women's Genetics 0414 CGENMOUSEEXT31133951 2. 68 DllBwg0414e expressedDAK009365 Mm. 296150 4. 506 MAK10 homolog, amino-actd N-acetyttransferase subunit, CGENMquSEEXT3113238l 2. 67 MaklO (S. cerevfsiae) 0 AK021042 Mm. 253902 4. 117 CGENMOUSEEXT31048861 2. 65 PecaProptonyt-Cpenzyme A carboxlase, alpha potypepttde A AY046947 Mm. 23876 0. 730 CGEN_MOUSE_EXT_3104866_1 2. 64 2010204I15Rlk RIKEN cDNA 2010204I15 gene0 AK008434 Mm. 245830 0. 748 CGEN_MOUSE_3006609_1 2. 64 Cldn 11 Claudin 11 E NM_008770 Mm. 4425 2. 534 CGEN_MOUSE_EXT_3107567_1 2. 64 Carhspl Calcium regulated heat stable protein i A NM_025821 Mm. 142095 1. 341 CGEN MOUSE 3002491 1 2. 64 Trpi2 _ Thyrold hormone recepter Intera*or 12 A _ AF033665 Mm. 209265 0. 491 CGEN_MOUSE_3004784 1 2. 62 Skbi SKB1 homolog (S. pombe A AF167573 Mm. 196585 2. 055 CGEN_MOUSE_EXT_3106379_1 2. 61 Sicl2a6 RIKEN cDNA E330013P08 ene E AF211854 Mm. 261614 0. 915 CGEN_MOUSE_3001652_1 2. 60 Cstf2t Cleavage stimulation factor,3're-RNA subunit 2, tau A AF322194 Mm. 22031 4. 442 CGEN_MOUSE 3002505_1 2. 60 Carl 4 Carbonic anhydrase 14 _ C NM_011797 Mm. 306954 2. 153 CGEN MOUSE 3006738 1 2. 59 Cnn2 Calponin 2 A NMF007725 Mm. 157770 0. 679 CGEN_MOUSE 3004441_1 2. 59 Ncoa4Muctear receptor coactfvator 4ANM019744 Mm. 275762 4. 826 CGEMMOUSEBg'3108582l 2. 59 2400003B06Rik RIKEN cDNA 2400003B06 ene B NM 026211 Mm. 45233 5. 600 CGEN_MOUSE_EXT_3114152_1 2. 59 Eif4b Eukaryotic translation Initiation factor 4B A BC007171 Mm. 290022 3. 178 CGEN_MOUSE_EXT_3110052_1 2. 59 Snx4Sorting nex) n 4ABC006043 Mm. 28196 2. 293 ATP-binding cassette, sub-family B (MDR/TAP), member CGENMquSE3002903l 2. 58 AbcblO10EMM019552 Mm. 274243 2. 662 CGEN MOUSE EXT 3106101 1 2. 58 Unknown EST no rot BC006884 0. 921 CGEN_MOUSE_300i802_1 2. 57 Etfi Eukaryotic translation terminatton factor 1 A D87691 Mm. 329353 4. 103 CGEN-MOUSE 3005296 1-2. 57 Cldn7 Claudin 7 E NM 016887 Mm. 281896 2. 494 CGEN_MOUSE_3001844_1 2. 56 Tc i T-com iex rotein 1 A NM 013686 Mm. 32019 3. 218 CGEMMOUSE30048121 2. 55 Ptn Plelotrophin B _ _ D90225 Mm. 279690 5. 017 CGEN MOUSE 3004210 1 2. 55 Tmpo Thymopoletin A NM 011605 Mm. 159684 0. 051 CGEN_MOUSE 3003123_1 2. 55 Pgrmcl Progesterone receptor membrane component 1 D NM U167S3 Mm. 9052 4. 193 CGEN_MOUSE EXi'3112121 1 2. 54 Cdca8 Cell division cte associated 8 A AK003755 Mm. 28038 4. 021 CGEN MOUSE EXT 3105359_1 2. 54 4933435A13Rlk RIKEN cDNA 4933435A13 gene A AK017063 Mm. 29536 1. 285 CGEN_MOUSE.. EXTI_3105541 1 2. 53 Zfp3l9 Zinc finger protein 319 A NM 024467 Mm. 29069 0. 939 CGENMOUSE30047171 2. 53 Pppicb Proteln phosphatase 1, catalytic subunOt, beta isoform AM27073 Mm. 241931 3. 771 CGEN MOUSE EXT 3107863 1 2. 53 Pbl RIKEN cDNA 2310032M22 gene A AK009582 Mm. 103058 3. 754 CGEN MOUSE EXT 3106277_1 2. 52 Ssrl Signal sequence receptor, alpha C NM_025965 Mm. 138725 4. 812 CGEN_MOUSE_EXT_3100165_1 2. 52 Gpr89 G proteln-coupled receptor 89 E BC010729 Mm. 46722 2. 491 CGEN_MOUSE_3002609_1 2. 52 Dhrs8 Dehydrogenase/reductase (SDR famii member 8 C AF304306 Mm. 46019 0. 023 CGEN_MOUSE_3005251_1 2. 52 Nrpl RIKEN cDNA D030005H02 gene C _ NM 008737 Mm. 271745 1. 712 A disintegrin-like and metalloprotease (reprolysin type) CGEN MOUSE EXT 3112448 1 2. 51 Adamtsl with thrombospondin type 1 motif,1 B NM_009621 Mm. 1421 0. 409 CGEN_MOUSE_EXT_3109526_1 2. 51 Scol SCO cytochrome oxidase deflcient homolog 1 (yeast) A AK018523 Mm. 129731 2. 914 CGEN-MOUS-3108870-1 2. 51 D930040F23Rlk RIKEN cDNA 4631424J17 gene 0 AK014534 Mm. 200947 0. 728 CGEN_MOUSE_EXT_3108744_1 2. 51 4931400A14Rlk RIKEN cDNA 4931400A14 gene A AK016419 Mm. 194450 1. 898 CGEN_MOUSE_EXT_3108283_1 2. 51 2310058AllRik RIKEN cDNA 2310058A11 gene A BC003199 Mm. 18834 4. 252 CGEN MOUSE 3001793 1 2. 48 Eef2 Eukaryotic translatton elongation factor 2AM76131 Mm. 289431 1. 069 CGEN MOUSE EXT 3108503 1 2. 45 1110018G07Rik (tIKEN cDNA 111i8G07 ene O SC006074 Mm. 24446 0. 861 CDP-dtacylglycerol--inositol 3-phosphattdyttransferase CGEN MOUSE EXT 3114036 1 2. 45 Cdipt (phosphattdylinositol synthase) E AK003041 Mm. 28219 0. 880 CGEN_MOUSE_3005121_t 2. 45 Unknown EST N/A NM_019751 1. 248 Solute carrier family 37 (glycerol-3-phosphate CGEN_MOUSE_EXT 3109680_t 2. 45 Slc37a3 transporter), member 3 E BC005744 Mm. 277527 0. 206 CGENMOUSEEXT31041071 2. 45 2810422B04Rik RIKEN cDNA 2810422B04gene B AK013131 Mm. 30256 3. 590 CGEN MOUSE EXT 3105813_1 2. 44 Pawr PRKC, apoptosis, WT1, regulator A AF377871 Mm. 336104 3. 199 CGEN_MOUSE_EXT_3114075_1 2. 44 1810011K17RIk RIKEN cDNA 1810011K17 gene A BC002098 Mm. 21520 4. 807 CGENMOUSE30018281 2. 43 Ddx25 DEAD (Asp-Glu-Ala-Asp) box polvpePtide 25 F NM_013932 Mm. 291723 1. 078 CGEN_MOUSE_30û4465_1 2. 43 Nmycl Neuroblastoma myc-related oncogene 1 A NM 008709 Mm. 16469 0. 580 CGEN MOUSE 3003991 1 2. 42 Abcd3 ATP-bindin cassette, sub-famlly D (ALD), member 3 E NM 008991 Mm. 194462 2. 104 CGEN_MOUSE_ExT_3103764_1 2. 42 3110043309Rlk RIKEN cDNA 3110043109 ene A BC005563 Mm. 128411 2. 402 CGEN_MOUSE_EXT_3106138_1 2. 42 Unknown EST A AK005923 2. 554 CGEN_MOUSE_3002878_1 2. 41 Rcl1 RNA terminal Phosphate cyclase-like 1 A NM_02i525 Mm. 28630 1. 783 CGENMOUSEEXT31139561 2. 41 DllErtd603e DNA segment, Chr 11, ERATO Do) 603, expressed0 MM026023 Mm. 276504 4. 075 CGEN MOUSE EXT 3111199 1 2. 41 Csnkla2 Caseln kinase 1, qamma 2 A BC004839 Mm. 29873 2. 955 CGEN_MOUSE_3003445_1 2. 41 Apim2 Adaptor proteln complex AP-1, mu 2 subunit A NM_009678 Mm. 22239 0. 244 CGEN MOUSE EXT 3104833 1 2. 41 Rif1 DNA seament, Chr 2, ERATO Dot 145, expressed 0 AK018316 Mm. 254530 3. 320 CGEN_MOUSE_EXT_3105121_t 2. 41 Unknown EST no rot BC005710 1. 950 CGEN_MOUSE_EXT_3104001_1 2. 40 Rbb7 Retinoblastoma binding protein 7 A NM 009031 Mm. 270186 5. 276 CGEN_MOUSE EXT_3106194_1 2. 40 D19Ertd737e DNA segment, Chr 19, ERATO Doi 737, expressed A AK011404 Mm. 290183 3. 991 CGEN MOUSE 3005921 1 2. 38 Cater) Calcitonin receptor-like _ E NM_018782 Mm. 75467 1. 179 CGEN_MOUSE_EXT 3104401_1 2. 38 1700081D17Rlk RIKEN cDNA 1700081D17 gene B AK006964 Mm. 23509 5. 854 CGEN_MOUSE 3000692_1 2. 38 Napil4 Nucleosome assembly prote ! n 1-like 4 A NM_008672 Mm. 294625 0. 205 CGEN MOUSE EXT 3104871 1 2. 38 Tbc1dl5 TBC1 domain family, member 15 _ _ A NM_025706 Mm. 22252 0. 771 CGEN MOUSE 3004372 1 2. 38 Gopc Gol i associated PDZ and colled-coll moUf contalning 0 AF287893 Mm. 155704 0. 209 CGEN_MOUSE EXT_3104242_1 2. 37 Mgat2 Mannoside acetylglucosaminyltransferase 2 D BC010583 Mm. 206642 3. 846 CGEN_MOUSE_EXT_3100180_1 2. 37 Hbid2 HESB like domain containing 2 A AK007415 Mm. 7884 3. 904 CGEN_MOUSE_3002839_1 2. 37 Mlnppl Multiple inositol polyphosphate hWdine PhosPhatase 1 B NM_010799 Mm. 255116 1. 446 CGENMOU5EEXT31043891 2. 37 Zmyml Zinc flnger, MYM domain containing 1 A NM 026670 Mm. 273806 5. 698 CGEN MOUSE 3003489_1 2. 37 Gcsl Glucosidase 1 D N M_020619 Mm. 28188 0. 674 CGEN_MOUSE_EXT_3106674_1 2. 36 A630007BC6Rik RIKEN cDNA A630007B06 gene no rot AK007628 Mm. 131555 2. 332 CGEN MOUSE 3000514 1 2. 36 Rrm2 Rlbonucleotide reductase M2ANM009104 Mm. 99 4. 912 CGEN_MOUSE_EXT_3106572_1 2. 36 Efhal Ef hand domain family A1 F AK014778 Mm. 26834 5. 274 CGEN_MOUSE_EXT_3106482_1 2. 36 4930579AllRik RIKEN CDNA4930579A11 geneEMM029478 Mm. 243797 3. 334 Phosphortbosyt pyrophosphate synthetase-assodated A AK011290 Mm. 25125 3. 518 CGEN_MOUSE_EXT_3113831_1 2. 36 Tubgl Tubulin amma 1 A BC006581 Mm. 142348 1. 802 Non imprtnted in Prader-Willf/Angelman syndrome 2 CGEN MOUSE_EXT 3104598 1 2. 36 Ni a2 homolo human E NM 023647 Mm. 333893 3. 308 CGEN MOUSE 3005641 1 2. 35 Grbl4 Growth factor receptor bound protein 14 A NM_016719 Mm. 214554 0. 227 CGEN_MOUSE 3001882_1 2. 35 Vapa Expressed sequence AA517753 D NM 013933 Mm. 266767 0. 503 CGEN_MOUSE_EXT_311065S_1 2. 35 Cnot8 CCM-NOT transcriptZon complex, subunit 8 A N M_026949 Mm. 28910 4. 813 CGENMOUSE30009431 2. 34 Yyl YY1 transcrtotton factorANM009537 Mm. 3868 2. 200 CGEN_MOUSE_3001863 1 2. 34 C*5 Chaperonin subunit 5 (epsilon) A NM_007637 Mm. 282158 3. 857 CGEN_MOUSE 3000460 1 2. 33 Adss2 Adenylosuccinate synthetase 2, non muscle A NM_007422 Mm. 338021 4. 584 CGEN MOUSE_EXT_3109148 1 2. 33 lam3 3unctlon adheston molecule 3 C NM 023277 Mm. 28770 2. 511 CGEN MOUSE EXT 3106620 1 2. 32 Zdhhcl3 Zinc ftnger, DHHC domain contatning 13 E AK010382 Mm. 279116 0. 716 CGENMOUSEEXT31042941 2. 32 Edeml ER de radation enhancer mannosidase al ha-Iike 1 D A8042828 Mm. 21596 1. 163 CGEN MOUSE 3000487 1 2. 31 Rfc2 Repilcatton factor C (activator 1) 2 NM020022 Mm. 332739 1. 914 CGEN MOUSE EXT 3105661 1 2. 31 1810043312RIk GangIloside-Induced differentiatton-associated-proteln 9 F AK007760 Mm. 25223 1. 413 CGEN_MQUSE EXT_3113606 1 231 BC003885 CDNA se uence BC003885 A BC003885 Mm. 312227 4. 569 Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase CGEN MOUSE 3005940 1 2. 31 Ywhah activation protein, eta polypeptide A NM011738 Mm. 332314 6. 077 CGEN-MOUSE, 3006285 1 2. 30 Cd81 CD 81 antigen E X59047 Mm. 806 4. 821 CGEN MOUSE EXT 3113241 1 2. 30 Mmsl91 MMS19 (MET18 S. cerevislae)-like A NM 028152 Mm. 218940 0. 648 CGENMOUSE30017061 2. 30 Hnrpal Heterogeneous nuclear ribonucleoprotein A1 A NM 010447 Mm. 299367 0. 826 CGEN MOUSE EXT 3108509 1 2. 30 Kpnb3 Karyopherin importln) beta 3 0 AF294327 Mm. 221452 5. 101 CGEN MOUSE EXT_3113934 1 2. 29 Ptchi Patched homo ! no rot AK020715 Mm. 228798 4. 480 CGEN_MOUSE_3000349_1 2. 29 Idhl Isocitrate dehydrogenase 1 (NADP+), soluble A NM010497 Mm. 9925 0. 208 CGEN_MOUSE_3004500_1 2. 28 Igfbp3 Insultn-like growth factor binding protein 3 B NM_008343 Mm. 29254 0. 371 CGEN MOUSE 3002064 1 2. 28 Gnal3 Guanine nucleotide binding protetn, alpha inhibitin 3 AU38502 Mm. 271703 1. 158 CGEN_MOUSE_3000874_1 2. 28 Tfdpl TranscriPusn fa*or Dp 1 A NM 009361 Mm. 925 4. 675 CGEN_MOUSE_EXT_3104270_1 2. 28 Idll Isopentenyl-diphosphate delta Isomerase A BC004801 Mm. 29847 5. 290 CGEN MOUSE EXT 3104254 1 2. 28 Laptm4b Lysosomal-associated protein transmembrane 4B E AF317418 Mm. 197518 5. 160 CGEN_MOUSE_3004781_1 2. 27 Ccni clln I A NM 017367 Mm. 250419 4. 334 CGEN MOUSE DCT 3105153 1 2. 27 4921532K09Rlk RIKEN cDNA 4921532K09 gene A AK014996 Mm. 292021 0. 780 CGEN_MOUSE_3004779_1 2. 27 Capt CAP, adenYlate cyclase-assoclated proteln 1 (yeast) A NM_007598 Mm. 8687 1. 323 CGENMOUSE30012681 2. 27 Tdl2 RIKEN cDNA E430034C17 gene A NM_011544 Mm. 171615 2. 755 CGENMOUSEEXT31110471 2. 27 DllErtd707e DNA segment, Chr 11, ERATO Dot 707, expressedANM025918 Mm. 277638 3. 744 CGEN_MOUSE_EXT_3104873_1 2. 26 2600016B03Rik RIKEN cDNA 2600016B03 gene A BC013079 Mm. 289818 5. 080 Methylenetetrahydrofolate dehydrogenase (NADP+ dependent), methenyltetrahydrofolate cyclohydrolase, CGEN_MOUSE EXT_3111721_1 2. 26 Mthfdl formyltetrahydrofolate synthase A BC008523 M m. 29584 4. 827 CGEN_MOUSE_EXT 3114372_1 2. 26 9430073N08Rik RIKEN cDNA 9430073N08 gene C AK020485 Mm. 30588 2. 550 CGEN MOUSE EXT 3111907 1 2. 26 5730454B08Rik RIKEN cDNA 5730454B08 gene A BC005786 Mm. 245357 2. 037 CGEN_MOUSE_EXT 3103239 1 2. 26 Cdcal Cell division cycle associated 1 A NM 023284 Mm. 151315 3. 416 CGEN MOUSE EXT 3112036 1 2. 25 Rab28 RAB28, member RAS oncogene family A BC004580 Mm. 41555 4. 921 CGEN MOUSE EXT 3109599 1 2. 25 AI642036 RIKEN cDNA C530049I24 gene 0 BC004080 Mm. 169673 5. 078 CGENMOUSEEXT31039921 2. 25 NuplO7 Nucleoporln 107 A BC004655 M m. 12568 4. 426 Solute carrierfamily 40 (iron-regulated transporter), 2. 24 Slc40al member 1 0 NM 016917 Mm. 28756 4. 125 CGEN MOUSE EXT 3112541 1 2. 23 Sas Sarcoma a mnlIfled sequence E NM_025982 Mm. 35650 5. 593 CGEN_MOUSE_EXT_3108811_i 2. 23 C330016H24Rlk RIKEN cDNA C330016H24 gene 0 AK014885 Mm. 253771 0. 006 llall cytotoxic granule-associated RNA binding protein-like CGENMOUSEEXT31093221 2. 23 Tiali 1 no match AK020218 Mm. 242072 1. 694 CGEN MOUSE EXT 3103795 1 2. 23 MyhllMvosin heayy cha) n 11, smooth musdeANM013607 Mm. 250705 5. 670 CGEN_MOUSE_3006264_1 2. 23 Bysl Bystin-like A NM 016859 Mm. 27291 2. 048 CGENMOUSE30021061 2. 23 MlP MARCKS-like proteln A NM_010807 Mm. 2769 1. 497 CGENMOUSEEXT31116261 2. 23 2 nla5 Zinc fln er rotein subfamil 1A 5 no rot AK009564 Mm. 334273 3. 326 CGEN_MOUSE_3004514_1 2. 22 Mdm2 Transformed mouse 3T3 cell double minute 2 A NM 010786 Mm. 22670 1. 000 CGEN MOUSE_EXT_3113899_1 2. 22 150001S06Rik RIKEN cDNA 1500011306 qene 0 BC008229 Mm. 276341 5. 820 SMC2 structural maintenance of chromosomes 2-like 1 CGEN_MOUSE_3004771_1 2. 22 Smc211 (Yeast) A NM_008017 Mm. 2999 1. 076 CGEN MOUSE 3003604 1 2. 22 Sna 23 S na tosomal-assoclated rotein 23 A NM QQ9222 Mm. 245715 2. 910 CGEN_MOUSE_EXT_3108851_1 2. 21 Poldip2 Polymerase (DNA-directed), delta Interacting protein 2 F NM_026389 Mm. 197493 3. 201 CGENMOUSE30019621 2. 21 Sdf2l1 Stromal ceil-derived factor 2-like 1 B AB043006 Mm. 30222 0. 249 CGEN_MOUSE_EXT_3114509_1 2. 21 Bid BH3 Interacting domain death agonlst no_prot AK012404 Mm. 235081 3. 310 CGEN MOUSE EXT 3113509 1 2. 21 1700022N24Rik RIKEN cDNA 1700022N24 gene E BC014812 Mm. 136973 3. 546 CGEN_MOUSE EXT_3112271_1 2. 20 Cnn3 _ Calponin 3, acidlc A AK005460 Mm. 275555 4. 825 CGEN MOUSE 3005126 1 2. 20 Thbsl Thrombospondin 1 B NM_011580 Mm. 4159 0. 890 CGENMOUSEEXT31120401 2. 20 Farsla Phenylalanine-tRNA sYnthetase-liket alpha subunit A BC006862 Mm. 292517 3. 076 CGEN MOUSE_EXT 3111444_1 2. 20 Snx5 Sorting nexin 5 _ _ no_prot AF357317 Mm. 273379 3. 005 CGEN_MOUSE_EXT 3112686 1 2. 20 2510002A14Rlk RIKEN cDNA 2510002A14 qene 0 AK010886 Mm. 260594 2. 533 CGEN MOUSE EXT 3114167 1 2. 20 Pnrc2 Proline-rich nuclear receptor coactivator 2 A NM 026383 Mm. 29159 4. 14Z CGENMOUSEEXT31110431 2. 20 Lix1 Umb expresslon 1 homolog (chicken) A NM_025681 Mm. 268018 2. 194 CGEN_MOUSE_EXT_3105704_1 2. 20 Unknown EST no_prot Y12656 4. 783 CGEN_MOUSE_3005384 1 2. 19 Map2k6 Mitogen a*lvated proteín kinase kinase 6 A U39066 Mm. 14487 0. 495 CGEN_MOUSE 3006306 1 2. 18 Batla HLA-B-associated transcript 1A A NM 019693 Mm. 126043 3. 477 Protefn phosphatase 1B, magnesium dependent, beta 2. 18 Ppmlb isoform A U09218 Mm. 249695 1. 986 CGEN_MOUSE_EXT_3112240_1 2. 17 Wrd43 WD repeat domaln 43 no prot AK012043 Mm. 257762 0. 946 CGEN_MOUSE_3000818_1 2. 17 Foxf2 Forkhead box F2 F NM_010225 Mm. 243661 3. 888 CGEN_MOUSE_EXT_3106093_1 2. 17 Rps6ka6 Ribosomal protein S6 kinase polypeptide 6 A AK012150 Mm. 37617 3. 441 CGEN_MOUSE_EXT_3110047_1 2. 17 Rpnl RibophorXn I ~ C BC002175 Mm. 188544 4. 947 CGEN MOUSE DCf 3107185_1 2. 17 2610311I19Rlk RIKEN cDNA 2610311I19 qene E NM_023311 Mm. 270382 5. 395 CGEN MOUSE 30015091 2. 16 Zfpl46 Zfncflnger protein 146 A NM 011980 Mm. 42054 1. 231 CGENMOUSEEXT31125901 2. 16 Amotil AnatomoHn-Xke 1noprptAK010096 Mm. 159552 4. 923 CGEN MOUSE EXT 3103771 1 2. 16 Mvipf Myosin light chain, phosphorylatabfe, fast skeletal muscle A NM 016754 Mm. 14526 2. 319 CGEN MOUSE 3002390 1 2. 16 Dld Dlhydrotipoamide dehydrogenase A NM 007861 Mm. 3131 4. 252 CGEN_MOUSE_DCf_3110996 1 2. 16 Zf364 Zinc flnger protein 364 A NM 026406 Mm. 26194 0. 990 Protein kinase, AMP-activated, gamma 2 non-catalytic CGEN_MOUSE_EXT_3112113_1 2. 15 Prkag2 subunit A BC015283 Mm. 33649 3. 022 DNA segment, Chr 3, University of California at Los CGEN_MOUSE_3007359_1 2. 15 D3UdalAngetes 1DAB041655 Mm. 29702 5. 316 CGEN_MOUSE_30029861 2. 15 Rb 4 Retinol binding protein 4plasma B U63146 Mm. 2605 2. 053 CGEN MOUSE EX1'3107725 1 2. 14 Zdhhc6 Zinc finger, DHHC domain containing 6ENM025883 Mm. 370235 4. 186 CGEN_MOUSE_3001288_1 2. 14 Unknown EST A ABO10307 0. 051 CGEN_MOUSE_3003987_1 2. 13 Pxmp3 Peroxisomal membrane protein 3 A NM 008994 Mm. 132336 3. 758 CGEN_MOUSE_3006086_1 2. 13 E430034L04Rlk RIKEN cDNA E430034L04 ene A NM 011816 Mm. 290530 6. 171 CGEN MOUSE 3002025 1 2. 13 Calr Calreticultn B NM 007591 Mm. 1971 2. 365 CGEN MOUSE EXT 3110625 1 2. 13 2810013P06Rik RIKEN cDNA 2810013P06 genenoprotAK012741 Mm. 294938 2. 035 CGEN MOUSE 3002161 1 2. 13 Metap2 Methlonlne amlnopeptidase 2 A NM_019648 Mm. 289329 3. 380 CGEN MOUSE 3001582 1 2. 13 Ncorl RIKEN cDNA 5730405M06 qene A NM_011308 Mm. 271814 4. 304 CGENMOUSEEXT31107661 2. 12 Aars Alanyl-tRNA synthetase A BC013261 Mm. 24174 2. 724 CGENMOUSE300525012. 12 Fath Fat tu mor suppressor homoloq (Drosophila) no_prot A i250768 Mm. 27365 0. 145 CGEN_MOUSE_EXT_3109501_1 2. 12 Tsfm RIKEN cDNA 2310050B20 gene B AK020437 Mm. 29900 5. 196 CGEN MOUSE 3006198 1 2. 12 Ddx1 DEAD (Asp-Glu-Ala-AsP) box polypeptide 1 A A7223068 Mm. 251255 0. 477 Smu-1 suppressor of mec-8 and unc-52 homolog (C. CGENMOUSE30047251 2. 11 Smul elegans) A NM 021535 Mm. 289929 1. 845 CGEN MOUSE EXT 3112765 1 2. 11 0610011D08Rik RIKEN cDNA 0610011D08 gene B NM 025647 Mm. 294159 3. 839 CGEN_MOUSE_EXr_3107524_1 2. 11 2310022K01Rik RIKEN cDNA 2310022K01 genenomatch AK009476 Mm. 290410 1. 096 CGEN MOUSE EXT 3112550 1 2. 11 Ddx42 DEAD (Asp-Glu-Ala-Asp) box polypeptide 42 A AK007805 Mm. 41367 2. 365 CGEN MOUSE 3001638 1 2. 11 Myef2 Myelin bask proteln expression Fa*or 2, repressor A U13262 Mm. 299755 0. 772 CGEN_MOUSE_EXT_3106587_1 2. 10 Rab8a RAB8A, member RAS oncogene fa milY A NM_023126 Mm. 162811 3. 223 CGEN MOUSE 3001628 1 2. 10 Hnrpl Heterogeneous nuclear ribonucleoprotein L A AB009392 Mm. 9043 4. 913 CGENMOUSEEXT31040821 2. 10 Hsdllb2 Hydro sterold 11-beta dehydrogenase 2 E NM 008289 Mm. 5079 2. 224 CGEN MOUSE 3002621 1 2. 10 Gnpat Glyceronephosphate 0-acyltransferase A NM 010322 Mm. 29114 1. 733 CGEN_MOUSE_EXT_3110961_1 2. 10 Robo2 Roundabout homolog 2 (Drosophila no rot AK011091 Mm. 171736 3. 841 CGEN MOUSE EXT 3105224 1 2. 10 Gtf2h3 General transcriptton factor IIH, polYpeptide 3, 34kDa A AK017176 Mm. 185467 4. 510 CGENMOUSE30046321 2. 09 Radi RAD1 homolog (S. pombe) A NM011232 Mm. 38376 4. 019 CGEN_MOUSE_3000762_1 2. 09 Wsbl WD repeat and SOCS box-containing 1 A NM 019653 Mm. 307022 2. 996 CGEN_MOUSE_3003039_1 2. 09 Abcfl ATP-binding cassette, sub-family F (GCN20), member 1 0 AF213383 Mm. 329022 1. 661 CGEN_MOUSE_EXT_3112782 1 2. 09 5730406I15Rik RIKEN cDNA 5730406115 gene E NM_025668 Mm. 30043 5. 063 CGEN MOUSE 3004461 1 2. 09 RVk Receptor-like tyrosine kinase C L21707 Mm. 335391 4. 289 CGENMOUSE30024601 2. 08 Phgdh 3-phosphoglycerate dehydrogenase 0 L21027 Mm. 324382 1. 167 CGEN MOUSE EXT 3105338 1 2. 08 Rbml8 RNA bindlng motiF proteln 18 A NM_026434 Mm. 205937 2. 974 CGEN MOUSE EXT 3106305 1 2. 08 Unknown EST A A1278435 2. 679 CGEN MOUSE 3002280 1 2. 08 Fbxo8 F-box only protein 8 A Nom 915791 Mm. 251174 0. 724 CGENMOUSEEXT31094961 2. 08 1600012K10Rik RIKEN cDNA 1600012K10 gene A AK005431 Mm. 249356 0. 396 Transmembrane protein with EGF-like and two folltstatin- CGEN_MOU5E_3006244_1 2. 07 Tmeffl like domains 1 0 AJ400622 Mm. 130982 3. 618 CGENMOUSEEXT31120691 2. 07 Pbx1 Pre B-cell leukemia transcription factor 1 noprot AK009939 Mm. 43358 5. 116 CGEN_MOUSE_EXT_3109860_1 2. 07 Unknown EST A AK002480 2. 125 CGEN_MOUSE_EXT_3112749_1 2. 07 Sh3kbpl _ SH3-domaln kinase bAnding proteln 1 A NM_021389 Mm. 286495 0. 244 CGEN MOUSE EXT 3110455 1 2. 06 2400003C14Rik RIKEN CDNA2400003C14 geneAAK010262 Mm. 290036 1. 807 CGEN_MOUSE_EXT_3105700_l 2. 06 Zfa Zinc fin er rotetn autosomal A NM_009540 Mm. 347574 1. 706 CGEN MOUSE 3004590_1 2. 06 Btgl B-cell translocation gene 1, anti-proliferative A L16846 Mm. 272183 4. 369 CGEN MOUSE EXT 3105968 1 2. 06 1110061004Rik RIKEN cDNA 1110061004 gene A BC012436 Mm. 197816 2. 567 CGENMOUSE30041671 2. 06 Capzb Capping proteln actin fllament) muscle Z-Iine, beta A NM 009798 Mm. 2945 3. 231 CGENMOUSEEXT31107481 2. 05 Metapl Methionyl aminopeptidase 1 A AK006484 Mm. 26833 2. 123 TPX2, microtubule-associated protetn homolog (Xenopus CGEN_MOUSE_EXT_3111085_1 2. 05 Tpx2 laevis) 0 AK011311 Mm. 291583 1. 643 CGEN_MOUSE_3007355_1 2. 05 Golga7 RIKEN cDNA 4930518F22 geneANM020585 Mm. 196269 2. 539 TAF5-like RNA polymerase II, p300/CBP-associated factor CGENMOUSEEXT31076201 2. 04 Taf51 (PCAF)-assoclated Fa*or F BC013550 Mm. 291777 0. 716 CGEN_MOUSE_3000351_1 2. 04 Idh2 Isocitrate dehydrogenase 2 (NADP+), mitochondrlal A NM_V3011 Mm. 246432 3. 441 CGEN MOUSE 3002077 1 2. 04 Narol NMDA receptor-requlated gene 1 A AF23762Z Mm. 275281 1. 292 CGEN MOUSE EXT 3104505_1 2. 04 Uxsl UDP-glucuronate decarboxylase 1 B AF399958 Mm. 201248 0. 741 CGEN_MOUSE_3001691_1 2. 04 Raly RIKEN cDNA C130057N11gene A L17076 Mm. 370200 4. 350 CGEN MOUSE EXT_3108784 1 2. 03 D030074EOlRik RIKEN CDNAD030074E01 gene0 AK017149 Mm. 273769 1. 560 CGEN_MOUSE_EXT_3105200_1 2. 03 5430432P15Rik RIKEN cDNA 5430432P15 gene no_prot AK017383 Mm. 249310 4. 169 CGEN MOUSE EXT 3111486 1 2. 03 Cknl Cockayne syndrome 1 homolog (human) A AK014517 Mm. 212208 4. 372 CGEN MOUSE 3004906 1 2. 02 Epb4. 114b DNA segment, Chr4, ERATO Doi 335, expressed A NM_019427 Mm. 28217 1. 677 CGENMOUSE30048321 2. 02 Cdc37 Cell division cycle 37 homolog (S. cerevislae) A NM_016742 Mm. 32331 0. 664 CGENMOUSEEXT31086251 2. 02 Ndufs2 NADH dehYdrogenase (ubiqulnone) Fe-S protein 2 0 BC003898 Mm. 21669 2. 649 CGEN_MOUSE_EXr_3103319_1 2. 02 Fipill FIP1 like 1 (S. cerevislae) _ _ A NM_024183 Mm. 272468 4. 179 CGEN MOUSE_EXT_3104358_1 2. 01 Psatl Phosphoserine aminotransferase 1 A BC004827 Mm. 289936 4. 224 Protein phosphatase 2 (formerly 2A), regulatory subunit A CGEN_MOUSE_EXT_3105959_1 2. 00 Ppp2rlb (PR 65), beb Isoform 0 AK010754 Mm. 7726 2. 078 CGEN MOUSE EXT 3108086 1 2. 00 4932442K08Rlk RIKEN cDNA 4932 i42K08 gene A NM_024203 Mm. 35039 0. 219 CGEN MOUSE EXT 3108446 1 2. 00 Rnf20 Ring flnger protein 20 no rot BC004593 Mm. 24765 3. 446 CGENMOUSEBCr3113782l 2. 00 Eif2b2 Eukaryotic translation In (tiation factor 2B, subunit 2 beta ABC003326 Mm. 29041 3. 940 CGENMOUSEEXT31088291 1. 99 Afg3) l AFG3 (ATPase family gene 3)-like 1 (yeast) E AF329695 Mm. 287475 2. 307 CGENMOUSE30039861 1. 99 Decr2 2-4-dienoyl-Coenzyme A reductase 2, peroxisomal A NM 011933 Mm. 292869 0. 967 Eukaryotic translation initiation factor 3, subunit 6 CGEN MOUSE_EXT_3105018 1 1. 99 Elf3s61 interactin rotein A A7310346 Mm. 206404 4. 302 CGEN_MOUSE_EXT_3113226 1 1. 98 Trim33 RIKEN cDNA 8030451N04 gene 0 AF220138 Mm. 195036 3. 900 CGEN_MOUSE_3005368 1 1. 98 Fgfr2 Fibroblast growth factor receptor 2 C M23362 Mm. 358595 1. 317 CGEN MOUSE 3001676 1 1. 98 Srrml Serine/arginine repetitive matrix 1 A NM 016799 Mm. 1963 3. 522 CGEN MOUSE 3005618 1 1. 98 AU014947 Rho GTPase activatino proteln 5 A NM_009706 Mm. 35059 2. 172 CGENMOUSEBCr3105881l 1. 97 Tcfe2a Transcription factor E2a 0 BC006860 Mm. 3406 1. 268 CGEN_MOUSE_EXr_3100380_1 1. 97 Bmprla Bone morphogenetic protetn receptor, t1A C U04672 Mm. 237825 0. 596 CGEN 3004415 1 1. 97 Aktl Thymoma viral proto-oncogene 1 A NM_009652 Mm. 6645 1. 621 CGEN_MOUSE_EXT_3109960_1 1. 97 Unknown EST 0 BC010499 3. 474 CGEN_MOUSE 3001660_1 1. 97 Exosc9 Exosome component 9 A NM_019393 Mm. 116711 3. 543 CGEN_MOUSE_3004101_1 1. 96 Des Desmin A _ L22550 Mm. 6712 4. 762 CGEN_MOUSE 3007250 1 1. 96 Tera Teratocarcinoma expressed, serine rich A NM019643 Mm. 18637 0. 998 CGENMOUSE30002701 1. 96 Ganab Alpha glucosidase 2 alpha neutral subunit B NM_008060 Mm. 3196 3. 094 Similar to Orphan sodium-and chloride-dependent neurotransmitter transporter NTTS (Solute carrier family 6 CGENMOUSEEXT31065701 1. 96 member 16) no_prot AK006640 Mm. 333842 0. 631 CGEN_MOUSE_EXT_31132V_1 1. 96 Unknown EST 0 278157 2. 800 CGEN_MOUSE 3004049 1 1. 95 Actrla ARP1 actin-related protein 1 homolog A (yeast) A NM016860 Mm. 3118 0. 843 CGEN_MOUSE_3003684 1 1. 95 Ari6 p2 ADP-ribosylatton factor-like 6 interacting protefn 2 E Nom019717 Mm. 175403 1. 248 CGEN_MOUSE_EXT_3111308_1 1. 95 2810043G13Rlk RIKEN CDNA2810043G13 gene noprot AK012898 Mm. 100168 0. 844 CGEN_MOUSE_EXT_3108554_1 1. 95 Pmpcb Peptidase (mitochondrial Processing) beta A AK013995 Mm. 301655 0. 541 CGEN MOUSE EXT 3112068 1 1. 94 AL024069Expressed sequence AL024069noprotAK017173 Mm. 187470 0. 148 CGENMOUSEEXT31130391 1. 94 Ski Sloan-Kettering viral oncogene homolog AK009316 Mm. 28520 4. 722 CGEN_MOUSE_EXT 3110484_1 1. 94 Pspcl Paraspeckle protein 1 A NM 025682 Mm. 20129 2. 184 CGEN_MOUSE_EXT_3105258_1 1. 94 2410075D05Rlk RIKEN cDNA 2410075D05 gene A AK010722 Mm. 294503 0. 292 DNA segment, Chr 16, Brigham & Women s Genetics 1543 CGENMOUSEEXT31038151 1. 94 D16Bwgl543e expressedA NM026202 Mm. 258985 1. 582 CGEN MOUSE 100559 1. 93 6330583M11Rik RIKEN cDNA 6330583M11 ene A NM 024465 Mm. 112632 0. 480 CGENMOUSE30030171 1. 93 SIcl6al Solute carrier family 16 (monocarboxylic acid E NM_009196 Mm. 9086 5. 260 transporters), member 1 CGENMOUSE30006611 1. 93 Unknown EST _ _ A NM_008252 2. 470 CGEN_MOUSE_3006726_1 1. 93 Laspl UM and SH3 protein 1ANM010688 Mm. 271967 2. 668 CGEN MOUSE 3001718 1 1. 93 EIf4a1 Eukarvotfctranslattoninitiation factor 4A1 A X03040 Mm. 328549 3. 805 CGEN MOUSE 3004644 1 1. 92 Sycp3 Svnaptonemal complex protein 3 A NM 011517 Mm. 297977 1. 649 CGEN_MOUSE_3002205_1 1. 92 Prep ProlYl endopeptgdase A NM_011156 Mm. 37294 3. 036 CGEN MOUSE EXT 3105264 1 1. 92 Unknown EST no rot AL358892 2. 034 Solute carrier famfly 3 (activators of dibasic and neutral CGEN MOUSE_EXT_3104453 1 1. 92 Slc3a2 amino acid transport), member 2 D NM008577 Mm. 4114 4. 990 CGEN MOUSE 3000463 1 1. 91Unknown EST0 MM0074112. 189 CGEN_MOUSE_EXT_3112458_1 1. 91 Z 307 Zinc flnger protein 307 A NM 023685 Mm. 296071 4. 361 CGEN_MOUSE_EXT_3107441_1 1. 91 Arpc4 Actin related protefn 2/3 complex, subunit 4 nomatchNM026552 Mm. 289306 1. 055 CGEN MOUSE_EXT_3112939_1 1. 90 Atpaf2 ATP synthase mitochondr (al Fl complex assembt factor 2 ABC013607 Mm. 41651 1. 882 CGEN MOUSE EXT 3106972 1 1. 90 1700022L09Rlk RTKEN cDNA 1700022L09 çene A NM_025853 Mm. 25410 2. 076 CGEN_MOUSE_EXT_3113761_1 1. 90 Mcic Mld-1-related chlorlde channel 1 E BC003247 Mm. 214545 3. 841 CGEMMOUSEEXT31095301 1. 89 3830408P06Rtk RIKEN cDNA 3830408P06 gene 0 BC005522 Mm. 29631 3. 452 GEN_MOUSE 3001874 1 1. 89 Dnaib6 Dna3 (Hsp40) homolog, subfamily B, member 6 A NM 011847 Mm. 290110 1. 135 CGEN_MOUSE_3004176_1 1. 89 Tmod3 Tropomodulin 3 A NM_016963 Mm. 38445 4. 195 CGEN MOUSE DCf_3107591 1 1. 89 SfrslO RTKEN cDNA 5730405G21 qene A NM_009186 Mm. 210352 0. 314 CGENMOUSE30012721 1. 89 Cnbpl Cellular nucleic acid binding protein 1 A NM 013493 Mm. 290251 4. 597 CGEN MOUSE 3004194 1 1. 89 Tfb2m Transcription factor 82, mitochondrial B NM 008249 Mm. 293529 2. 126 CGEN_MOUSE_3002599_1 1. 89 H d HydroxyprostagIandin dehydrogenase 15 NAD A NM 008278 Mm. 18832 0. 819 CGEN_MOUSE_EXT_3113887_1 1. 88 Mat2a Methlonine adenosYltransferase II, alpha A BC003451 Mm. 29815 2. 867 CGEN MOUSE EXT_3109270_1 1. 88 2210419D22Rlk RTKEN cDNA 2210419D22 gene no_prot AK008985 Mm. 321990 2. 364 CGEN_MOUSE_EXT_3112794_1 1. 88 Similarto cadherin 19, type 2 preproprotegn nonprot AK014965 Mm. 322070 1. 009 CGEN MOUSE EXT 3112456 1 1. 88 Unknown EST no prot M18260 0. 716 CGEN_MOUSE_EXT_3103765_1 1. 87 9130221D24Rlk RTKEN cDNA 9130221D24 gene A AK020284 Mm. 98630 3. 267 CGEN MOUSE EXT 3112147 1 1. 87 Rere RIKEN cDNA E23001ZJ19 ene no rot AK004046 Mm. 291274 3. 963 CGEN_MOUSE_3000578_1 1. 87 Hells RTKEN cDNA E130115121 gene A NM_008234 Mm. 57223 1. 320 CGENMOUSEEXT31091161 1. 87 BC003993 CDNA sequence BC003993 A NM 030560 Mm. 288151 2. 993 General transcription factor II E, polypeptide 1 (alpha CGEN_MOUSE_EXT_3105474_1 1. 87 Gtf2el subunit) A AKOlt543 Mm. 287795 0. 816 CGENMOUSEEXT31079401 1. 86 Pmpca Peptidase (mitochondrial processing) alpha B BC010810 Mm. 250359 3. 952 CGEN_MOUSE 3002811 1 1. 86 Gcic Glutamate-steine ligase catal ic subunit A U85498 Mm. 89888 4. 261 CGEN MOUSE EXT 3104644 1 1. 86 2410129H14Rik RIKEN cDNA 2410129H14 gene A AK010788 Mm. 38912 3. 243 CGEN MOUSE EXT 3113785 1 1. 86 Pst 1 RIKEN cDNA E030018320 gene _ A A3308965 Mm. 105331 4. 599 CGENMOUSEEXT31001081 1. 85 5730466H23RIk RIKEN cDNA 5730466H23 gene A AK019965 Mm. 178684 0. 035 CGENMOUSE30003401 1. 85 Pakl PhosphoQlycerate kinase 1 A NM_008828 Mm. 336205 2. 079 CGENMOUSE30044501 1. 85 Amfr Autocrine motillty factor tor E NM 011787 Mm. 34641 2. 890 CGEN MOUSE 3000663 1 1. 85 Brd4 Bromodomaln containing 4 ANM020508 Mm. 253518 1. 390 CGEN_MOUSE_EXT_3103865_1 1. 85 2410042D21Rlk RIKEN cDNA 2410042D21 gene A BC003216 Mm. 46449 4. 265 CGEN_MOUSE_EXT_3108008_1 1. 85 Vps26 Vacuolar proteln sorting 26 (yeast) A BC007148 Mm. 260703 3. 764 CGEN MOUSE EXT 3110521 1 1. 84 Ddx47 DEAD (Asp-Glu-Ala-Asp) box polypeptide 47 A BC006843 Mm. 166524 2. 591 CGEN_MOUSE EXT_3114432_1 1. 84 2810481F14Rik RIKEN cDNA 2810481F14 gene 0 AK014855 Mm. 312328 3. 048 DNA segment, Chr 8, Wayne State University 49, CGEMMOUSEEXr31Q5127l 1. 84 D8Wsu49e expressed C NM_028007 Mm. 334685 4. 122 CGEN_MOUSE 3004306_1 1. 83 Kifc5a Ktnesin family member C5B A MM016761 Mm. 335626 1. 170 CGEN_MOUSE_EXT_3105252_1 1. 83 Unknown EST A AF324883 0. 868 CGEN_MOUSE EXT_3112898_1 1. 83 Ddx27 DEAD (Asp-Glu-Ala-Asp) box polypeptide V A BC011321 Mm. 295031 1. 257 CGEN MOUSE 3005685 1 1. 83 Neti Neuroepithelial cell transforming gene 1 A NM 019671 Mm. 22261 2. 078 CGEN_MOUSE ExT 3100573_1 1. 83 2210412DO1Rik RIKEN CDNA2210412D01 gene F AK008906 Mm. 23914 1. 067 Phosphoribosylaminolmidazole carboxylase, phosphor (bosylaminoribosylaminolmidazole, CGEN_MOUSE_EXT_3105299_1 1. 83 Paics succinocarboxamide synthetase A NM_025939 Mm. 182931 2. 058 CGEN MOUSE EXT 3105705 1 1. 82 2610029D06Rik RIKEN cDNA 2610029D06 gene A AK019163 Mm. 273264 5. 234 CGEN_MOUSE_EXT_3113085_1 1. 82 2310067B10Rik RIKEN cDNA 2310067B10 ene 0 BC007157 Mm. 23168 1. 552 CGEN MOUSE EXT 3105108 1 1. 82 Mtap Methylthloadenosine phosphorylase A BC003858 Mm. 28500 1. 442 CGEN MOUSE 3000518 1 1. 82 Hnrphl Heterogeneous nuclear rlbonucleoproteln H1 A NM_021510 Mm. 21740 0. 939 CGEN_MOUSE EXT_3106189 1 1. 82 6130401J04Rik RIKEN cDNA 6130401304 gene A AK015348 Mm. 122430 3. 465 CGENMOUSE30064521 1. 82 DkklDtckkopf homobg 1 (Xenopus laevis) B NM 010051 Mm. 214717 0. 991 CGEN_MOUSE_3002556_1 1. 81 Efna2 Ephrln A2 B NM 007909 Mm. 1478 0. 029 CGEN MOUSE 3006780 1 1. 81 C80913 Expressed sequence C80913 A NM 011274 Mm. 23997 3. 128 CGEN_MOUSE_EXT_3103486 1 1. 81 Taccl Transform ng, acidtc coiled-coil containing protein 1 no rot AK019530 Mm. 308452 0. 680 CGEN_MOUSE_EXT_3112592_1 1. 81 Fbxo22 F-box only proteln 22 no_prot AK002745 M m. 276429 4. 177 CGEN_MOUSE_EXT_3112164_1 1. 80 Unknown EST A NM 008015 2. 295 CGEN_MOUSE_EXT 3109452_1 1. 80 5730528L13RIk RIKEN cDNA 5730528L13 gene A AK013199 Mm. 140749 1. 119 CGEN MOUSE EXT 3107144 1 1. 80 Dek DEK oncoqene (DNA bindinq) A AK007546 Mm. 131150 2. 511 CGEN MOUSE_EXT 3108843 1 1. 80 Plxnd 1 Plexin D1 0 AK018097 Mm. 3085 0. 933 CGEN_MOUSE_EXT_3105404_1 1. 80 Tdrdl Tudor domaln contalninq 1 A NM_031387 Mm. 247541 3. 602 CGEN MOUSE_EXT_3113566_1 1. 80 1810030007Rik RIKEN cDNA 1810030007 gene __ A AK007661 Mm. 15974 0. 172 CGENMOUSEEXT31045851 1. 80 Osgepil O-sialoglycoprotein endopeptidase-like 1 A AK011265 Mm. 185144 1. 638 CGEN_MOUSE_EXT_3107218_1 1. 80 Sf3a3 Spllcln factor 3a, subunit 3 A BC009141 Mm. 25779 1. 972 CGEN MOUSE_EXT_3109309 1 1. 80 0610025011Rlk RIKEN cDNA 0610025011 gene B NM_025799 Mm. 26625 1. 379 Table 4 Markers Murine gene Membrane Probe ID name Description Localisation RefSeq Mouse UniGene CGEN_MOUSE_EXT_3105707_1 Znf335 Zinc finger protein 335 0 AK007785 Mm.330776 BG071497 Ewsh Ewing sarcoma homolog (Ewsh) A NM_007968 Mm.142822 BG077268 Tcp1 t-complex protein 1 (Tcp1) A NM_013686 Mm.32019 BG078410 Eno1 enolase 1, alpha non-neuron (Eno1) A NM_023119 Mm.70666 tyrosine 3-monooxygenase/tryptophan 5- monooxygenase activation protein, theta polypeptide (CDK5 regulatory subunit associated BG084914 Ywhag protein 2) A NM_011739 Mm.289630 CGEN_MOUSE_3000542_1 Cyfip1 Cytoplasmic FMR1 interacting protein 1 A NM_011370 Mm.37249 Sine oculis-related homeobox 2 homolog CGEN_MOUSE_3001434_1 Six2 (Drosophila) A D83147 Mm.5039 Minichromosome maintenance deficient 7 (S. CGEN_MOUSE_3002684_1 McM7 cerevisiae) A NM_008568 Mm.241714 CGEN_MOUSE_3003427_1 Kpna2 Karyopherin (importin) alpha 2 A NM_010655 Mm.12508 CGEN_MOUSE_3003953_1 Hspa8 Heat shock protein 8 A M19141 Mm.336743 Ras-GTPase-activating protein SH3-domain CGEN_MOUSE_3006486_1 G3bp binding protein A NM_013716 Mm.39631 CGEN_MOUSE_3006486_1 Hoxa10 Homeo box A10 A NM_008263 Mm.5 CGEN_MOUSE_3006643_1 Crym Crystallin, mu (Crym) A NM_016669 Mm.9114 CGEN_MOUSE_EXT_3108113_1 2610312E17Rik RIKEN cDNA 2610312E17 gene A BC005755 Mm.5110 CGEN_MOUSE_EXT_3112558_1 Ogfr Opioid growth factor receptor (Ogfr) A NM_031373 Mm.250418 IMBCC001d15 Rara Retinoic acid receptor alpha (RAR#035) A NM_009024 Mm.103336 CGEN_MOUSE_3005773_1 Gdnf Glial cell line derived neurotrophic factor (GDNF) B NM_010275 Mm.4679 CGEN_MOUSE_EXT_3104439_1 Mesdc2 Mesoderm development candiate 2 B NM_023403 Mm.117365 CGEN_MOUSE_EXT_3105577_1 1300010F03Rik RIKEN cDNA 1300010F03 gene B AK004956 Mm.159651 CGEN_MOUSE_EXT_3107928_1 2810037C14Rik RIKEN cDNA 2810037C14 gene B NM_026034 Mm.260782 CGEN_MOUSE_3005251_1 Nrp1 Neuropilin-1 (Nrp1) C NM_008737 Mm.271745 CGEN_MOUSE_3005356_1 CD164 CD164 antigen C NM_016898 Mm.269815 CGEN_MOUSE_3005446_1 CD83 CD83 antigen (CD83) C NM_009856 Mm.57175 CGEN_MOUSE_3005725_1 Sdfr1 Stromal cell derived factor receptor 1 C NM_009145 Mm.15125 BG076069 / BG085134 CD24a CD24a antigen C NM_009846 Mm.29742 BG085206 / BG073524 Spint-2 Serine protease inhibitor, Kunitz type 2 (Spint-2) C NM_011464 Mm.295230 Tacstd1; Tacstd1; EGP; Ly74; TROP1; Egp314; Ep- CAM; Tacsd1; CGEN_MOUSE_3003658_1 GA733-2 Tumor-associated caicium signal transducer 1 C NM_008532 Mm.4259 MRK; Ryk; Vik; CGEN_MOUSE_3004461_1 ERK-3 Receptor-like tyrosine kinase C L21707 Mm.335391 Fgfr2; Bek; Fgfr7; Fgfr-2; CGEN_MOUSE_3005368_1 Fgfr-7; KGFRTr Fibroblast growth factor receptor 2 C NM_010207 Mm.16340 App; App; Adap; Cvap; Abeta; appican; CGEN_MOUSE_3005586_1 betaAPP Amyloid beta (A4) precursor protein C NM_007471 Mm.277585 Bmpr1a; ALK3; BMPR-IA; CGEN_MOUSE_EXT_3100380_1 1110037122Rik Bone morphogenetic protein receptor, type 1A C NM_009758 Mm.237825 Cda08-pending; Cda08-pending; DNA segment, Chr 8, Wayne State University 49, CGEN_MOUSE_EXT_3105127_1 2310047C21Rik expressed C NM_028007 Mm.334685 Ssr1; Ssr1; SSR; TRAPA; CGEN_MOUSE_EXT_3106277_1 2510001K09Rik Signal sequence receptor, alpha C NM_025965 Mm.138725 Jam3; Jam3; JAM-3; Jcam3; CGEN_MOUSE_EXT_3109148_1 1110002N23Rik Junction adhesion molecule 3 C NM_023277 Mm.28770 Ptk7; CGEN_MOUSE_EXT_3110229_1 8430404F20Rik PTK7 protein tyrosine kinase 7 C NM_175168 Mm.181833 IMBCC001c05 Cdh11 Cadherin 11 C NM_009866 Mm.1571 CGEN_MOUSE_3005338_1 Sdcbp Syndecan binding protein D NM_016807 Mm.247473 CGEN_MOUSE_3006543_1 Itm2c Integral membrane protein 2C D AB030199 Mm.29870 CGEN_MOUSE_EXT_3106833_1 Trim59 Tripartite motif-containing 59 D NM_025863 Mm.176695 Nsdhl; Nsdhl; CGEN_MOUSE_3002783_1 Bpa; Str; NAD(P) dependent steroid dehydrogenase-like D NM_010941 Mm.38792 H105E3; XAP104 D CGEN_MOUSE_3006165_1 Vamp3 Vesicle-associated membrane protein 3 (Intracellular) NM_009498 Mm.273930 Serp1-pending; RAMP4; SERP1; DNA segment, Chr 3, University of California at CGEN_MOUSE_3007359_1 D3Ucla1 Los Angeles 1 D NM_030685 Mm.29702 Slc3a2; Slc3a2; Solute carrier family 3 (activators of dlbasic and CGEN_MOUSE_EXT_3104453_1 Mdu1; Mgp-2hc neutral amino acid transport), member 2 D NM_008577 Mm.4114 CGEN_MOUSE_EXT_3108503_1 1110018G07Rik RIKEN cDNA 1110018G07 gene D NM_178065 Mm.24446 Purb, D11Bwg0414e; CGEN_MOUSE_EXT_3113395_1 2310015K15Rik Purine rich element binding protein B (purb) D BC019459 Mm.296150 Solute carrier family 6 (neurotransmitter CGEN_MOUSE_3003323_1 Slc6a6 transporter, taurine), member 6 E NM_009320 Mm.247352 CGEN_MOUSE_3005056_1 Gja1 Gap junction membrane channel protein alpha 1 E NM_010288 Mm.370184 CGEN_MOUSE_3006084_1 Tdel Tumor differentially expressed 1 E NM_012032 Mm.218473 CGEN_MOUSE_3006285_1 CD81 CD81 antigen E NM_133655 Mm.806 CGEN_MOUSE_EXT_3104480_1 Slc35f5 Solute carrier family 35, member F5 E Ak004892 Mm.28654 Solute carrier family 39 (Zinc transporter), CGEN_MOUSE_EXT_3106496_1 Slc39a7 member 7 E NM_008202 Mm.18556 CGEN_MOUSE_EXT_3114517_1 Grcc3f Gene rich cluster, C3f gene E AY028317 Mm.273915 BG082455 Cldn6 Claudin 6 E NM_018777 Mm.86421 Slc20a1; Slc20a1; Glvr1; CGEN_MOUSE_3002992_1 Givr-1 Solute carrier family 20, member 1 E NM_015747 Mm.272675 Slc16a1; Solute carrier family 16 (monocarboxylic acid Slc16a1; MCT1 transporters), member 1 E NM_009196 Mm.9086 Arl6ip2; Arl6ip2; Aip-2; CGEN_MOUSE_3003684_1 AV334690 ADP-ribosylation factor-like 6 interacting protein 2 E NM_019717 Mm.175403 CGEN_MOUSE_3004450_1 Amfr Autocrine motillty factor receptor E NM_011787 Mm.34641 CGEN_MOUSE_3005296_1 Cldn7 Claudin 7 E NM_016887 Mm.281896 Calcrl; Calcrl; CGEN_MOUSE_3005921_1 CRLR Calcitonin receptor-like E NM_018782 Mm.75467 CGEN_MOUSE_3006083_1 Tde2 Tumor differentially expressed 2 E NM_019760 Mm.29344 CGEN_MOUSE_3006158_1 Sypl Synaptophysin-like protein E NM_013635 Mm.246304 Cldn11; Cldn11; Osp; Otm; Claudin11; CGEN_MOUSE_3006609_1 Claudinh-11 Claudin 11 E NM_008770 Mm.4425 Gpr89, CGEN_MOUSE_EXT_3100165_1 4933412D19Rik G protein-coupled receptor 89 E NM_026229 Mm.46722 FAE; Elovl6; ELOVL family member 6, elongation of long chain CGEN_MOUSE_EXT_3100376_1 FAE; LCE fatty acids (yeast) E NM_130450 Mm.314113 CGEN_MOUSE_EXT_3103277_1 P2y5 Purinergic receptor (family A group 5) E AK011967 Mm.320228 Nipa2, 3830408P04Rik; 3830408P04Rik; Non imprinted in Prader-Willi/Angelman syndrome CGEN_MOUSE_EXT_3104598_1 2600017P10Rik 2 homolog (human) E NM_023647 Mm.333893 CGEN_MOUSE_EXT_3106482_1 4930579A11Rik RIKEN cDNA 4930579A11 gene E NM_029478 Mm.243797 CGEN_MOUSE_EXT_3107185_1 2610311I19Rik RIKEN cDNA 2610311I19 gene E (intracellular) NM_023311 Mm.270382 Zdhhc6; Zdhhc6; 2400007G07Rik; CGEN_MOUSE_EXT_3107725_1 5930409M18Rik Zinc finger, DHHC domain containing 6 E NM_025883 Mm.370235 Slc37a3; Slc37a3; Solute carrier family 37 (glycerol-3-phosphate CGEN_MOUSE_EXT_3109680_1 2610507021Rik transporter), member 3 E NM_028123 Mm.277527 CGEN_MOUSE_EXT_3112541_1 2700085A14Rik Sarcoma amplified sequence E NM_025982 Mm.35650 1700022N24Rik; 1700022N24Rik; CGEN_MOUSE_EXT_3113509_1 MGC19394 RIKEN cDNA 1700022N24 gene E NM_145355 Mm.136973 CGEN_MOUSE_EXT_3113761_1 Mclc-pending Mid-1-related chloride channel 1 E NM_145543 Mm.214545 BG066641 Scd2 Stearoyl-Coenzyme A desaturase 2 (Scd2) E (intracellular) NM_009128 Mm.193096 BG071792 1110034A24Rik RIKEN cDNA 1110034A24 gene F NM_027269 Mm.107180 CGEN_MOUSE_3001202_1 Hoxd13 Homeo box D13 F NM_008275 Mm.57227 no_class_predi BG073496 Rdh10 retinol dehydrogenase 10 (all-trans) (Rdh10) ction NM_133832 Mm.274376 CGEN_MOUSE_EXT_3106870_1 Sall4 Sal-like 4 (Drosophila) no_match AF285588 Mm.256916 Homeo box A11, opposite strand transcript CGEN_MOUSE_3000939_1 Hoxalls (Hoxalls) no_prot U20366 Um.360304 CGEN_MOUSE_EXT_3110204_1 Robo2 Roundabout homolog 2 (Drosophila) no_prot AK011188 Mm.171736 Table 5 Human homolog Full length human sequence gene name Human homolog gene symbol Human Unigene (example cDNA) ZNF335 zinc finger protein 335 Hs.174193 NM_022095.3 EWSR Ewing sarcome breakpoint region 1 Hs.374477 NM_005243.1 TCP1 T-complex 1 Hs.487054 BT006969.1 ENO1 enolase-1 Hs.517145 BT007163.1 SFN / YWHAQ stratifin / Ywhaq Hs.523718 / Hs. 74405 NM_006142.3 / AF070556 CYFIP1 Cytoplasmic FMR1 interacting protein 1 Hs.26704 BC001306.2 SIX2 Sine oculis-related homeobox 2 homolog (Drosophila) Hs.101937 NM_016932.3 MCM7 MCM7 minichromosome maintenance deficient 7 Hs.438720 NM_182776.1 KPNA2 Karyopherin alpha 2 (RAG cohort 1, importin alpha 1) Hs.252712 NM_002266.1 HSPA8 heat shock 70kDa protein 8 Hs. 180414 NM_006597.3 G3BP Ras-GTPase-activating protein SH3-domain binding protein Hs.3353 NM_198395.1 HOXA10 Homeo box A10 Hs.110637 BC071843.1 CRYM crystallin, mu Hs.924 LO2950.1 MEP50 methylosome protein 50 Hs.204773 NM_024102.2 OGFR opioid growth factor receptor Hs.67896 AF109134.1 RARA retinoic acid receptor alpha Hs.535499 NM_000964.1 GDNF Glial cell line derived neurotrophic factor Hs.248114 NM_000514.2 MESDC3 Mesoderm development candiate 2 Hs.549506 / 513070 BC007867.2 / BC012746.2 KIAA0564 KIAA0564 protein Hs.368282 BC053674.1 SVH SVH protein Hs.287412 BC003586.1 NRP1 neuropilin-1 Hs.131704 BT006995.1 CD164 CD164 antigen, sialomucin Hs.520313 AF106518.1 CD83 CD83 Hs.484703 NM_004233.2 SDFR1 Stromal cell derived factor receptor 1 Hs.187866 BC067828.1 CD24 CD24 precursor Hs.375108 BT007404.1 SPINT2 Serine protease inhibitor, Kunitz type 2 Hs.31439 CR407604.1 TACSTD1 Tumor-associated calcium signal transducer 1 Hs.692 NM_002354.1 PYK Receptor-like tyrosine kinase Hs.245869 X96588.1 Fibroblast growth factor receptor 2 (bacteria-expressed kinase keratinocyte growth factor receptor, craniofacial dysostosis 1, Crouzon syndrome, Pfeiffer syndrome, Jackson-Welss FGFR2 syndrome) Hs.533683 M80634.1 Amylold beta (A4) precursor protein (protease nexin-II, Alzheimer disease) APP (APP) Hs.4394980 AF2822435.1 BMPR1A, ALK-3 Bone morphogenetic protein receptor, type 1A Hs.524477 Z22535.1 cDA08 T-cell Immunomodulatory protein (CDA08) Hs.42217 Af212247.1 SSR1 Signal seguence receptor, alpha Hs.114033 BT007387.1 JAM3 Junction adhesion molecule 3 Hs.150718 Ak125071.1 PTK7 PTK7 protein tyrosine kinase 7 Hs.95072 NM_152883.1 CDH11 Cadherin 11, type 2, OB-cadherin (osteoblast) Hs.116471 NM_001797.2 SDCBP Syndecan binding protein (syntenin) Hs.200804 AK128645.1 ITM2C Integral membrane protein 2C Hs.111577 BC050668.1 TRIM59 Tripartite motif-containing 59 Hs.212957 NM_173084.1 NSDHL NAD(P) dependent steroid dehydrogenase-like Hs.57698 NM_015922.1 VAMP3 Vesicle-associated membrane protein 3 (cellulbrevin) Hs.66708 BT007327.1 SERP1 Stress-assoclated endoplasmic retculum protein 1 Hs.518326 AB022427.1 Solute carrier family 3 (activators of dibasic and neutral amino acid transport), SLC3A2 member 2 Hs.502769 NM_002394.3 KIAA0317 KIAA0317 protein Hs.497417 NM_014821.2 PURB Purine-rich element binding protein B Hs.349150 AY039216.1 Solute carrier family 6 (neurotransmitter transporter, SLC6A6 taurine), member 6 Hs.529488 NM_003043.2 GJA1 Gap junction protein, alpha 1, 43kDa (connexin 43) Hs.74471 NM_000165.2 TDE1 Tumor differentially expressed 1 Hs.272168 NM_006811.2 CD81 CD81 antigen (target of antiproliferative antibody 1) Hs.54457 NM-004356.2 SLC35F5 Solute carrier family 35, member F5 Hs.292509 BC050096.1 SLC39A7 Solute carrier family 39 (zinc transporter), member 7 Hs.278721 NM_006979.1 C3F Putative protein similar to nessy (Drosophila) Hs.530552 BT007000.1 CLDN6 claudin 6 Hs.533779 BT007399.1 SLC20A1 Solute carrier family 20, member 1 HS.187946 NM_005415.3 Solute carrier family 16 (monocarboxylic acid SLC16A1 transporters), member 1 HS.75231 NM_003051.2 ARL6IP2 ADP-riobosylation factor-like 6 interacting protein 2 HS.190440 BC053508.1 AMFR Autocrine motility factor receptor Hs.295137 BC051032.1 CLDN7 claudin 7 Hs.513915 AJ011497.1 CALCRL Calcitonin receptor-like Hs.470882 AY389506.1 TDE2 Tumor differentially expressed 2 Hs.146668 AF087902.1 SYPL Synaptophysin-like protein Hs.80919 NM_182715.1 CLDN11 Claudin 11 Hs.31595 AJ245901.1 GPR89 G protein-=coupled receptor 89 Hs.319301 BT006679.1 ELOVL family member 6, elongation of long chain fatty acids ELOVL6 (FEN1/Elo2, SUR4/Elo3-like, yeast) HS.412939 BC001305.1 P2RY5 Purinergic receptor P2Y, G-protein coupled, 5 Hs.123464 BC045651.1 NIPA2 Non Imprinted in Prader-Willi/Angelman syndrome 2 Hs.370367 BC011775.2 VMP1 Likely ortholog of rat vacuole membrane proteln 1 Hs.444569 BC053563.1 SMAP-5 Golgi membrane protein SB140 Hs.372050 AY358863.1 ZDHHC6 Zinc finger, DHHC domain containing 6 Hs.196990 NM_022494.1 Solute carrier family 37 (glycerol-3-phosphate transporter), SLC37A3 member 3 Hs.446021 BC046567.1 SAS Sarcoma amplified sequence Hs.50984 NM_005981.3 FLJ38628 hypothetical protein FLJ38628 Hs.517553 BC033166.1 MCLC Mid-1-related chloride chaqnnel 1 Hs.93121 BC002939.2 Similar to stearoyl-CoA desaturase; acyl-CoA desaturase; fatty acid dessturase; LOC400586 delta-9-desaturase Hs.512027 XM_375424.2 C14orf104 chromosome 14 open reading frame 104 Hs.231761 NM_018139.1 HOXD13 Homeo box D13 Hs.152414 NM_000523.2 RDH1 Retlnol dehydrogenase 10- (all-trans) Hs.244940 BC067131.1 SALL4 Sal-like 4 (Drosophlla) Hs.517113 AY170622.1 antisense of HOXA11 Antisence of HOXA11 Hs.249171 NM_005523.4 ROBO2 Roundabout homolog 2 (Drosophila) Hs.13305 BC064374.1 Table 6 Probe ID RefSeq Unigene Marker Cell Type Average Fold B-score Change (E10. 5 MMAM) BG078528 NM_013633 Mm. 17031 Oct-4 ES, EC 0. 742 0. 134 BG 067052 AF507043 Mm. 6047 Nanog ES, EC 1. 014-6. 800 BG085568 NM_133654 Mm. 29798 CD34 HSC, satellite, 1. 550-3. 230 endothelial progenitors BG087137 NM 021099 Mm. 4394 c-kit HSC, MSC 1. 018-6. 669 BG072793 NM 010738 Mm. 263124 sca-1 HSC, MSC 0. 931-4. 970 BG065276 NM_013723 Mm. 89918 Podacolyxin-like Haemangoblasts 0. 562 2. 073 BG066228 NM_016701 Mm. 23742 Nestin Neural progenitor 0. 729 0. 118