Abstract
The mammalian kidney arises from OSR1(+) progenitor cells in the intermediate mesoderm. However, these cells must acquire unique properties before they can respond to inductive signals that launch the differentiation program. Recent data indicate that the transcription factor, WT1, plays a master role in this transition. Interestingly, some of these embryonic nephron progenitor cells are retained in the adult organ where they may participate in tissue regeneration after acute kidney injury. A better understanding of the biology of these cells may one day allow progenitor cell-based therapeutic strategies to help regenerate damaged adult nephrons.
Similar content being viewed by others
References
Grobstein C (1956) Trans-filter induction of tubules in mouse metanephrogenic mesenchyme. Exp Cell Res 10:424–440
Wang Q, Lan Y, Cho ES, Maltby KM, Jiang R (2005) Odd-skipped related 1 (Odd 1) is an essential regulator of heart and urogenital development. Dev Biol 288:582–594
Mae S, Shirasawa S, Yoshie S, Sato F, Kanoh Y, Ichikawa H, Yokoyama T, Yue F, Tomotsune D, Sasaki K (2010) Combination of small molecules enhances differentiation of mouse embryonic stem cells into intermediate mesoderm through BMP7-positive cells. Biochem Biophys Res Commun 393:877–882
James RG, Schultheiss TM (2005) Bmp signaling promotes intermediate mesoderm gene expression in a dose-dependent, cell-autonomous and translation-dependent manner. Dev Biol 288:113–125
James RG, Kamei CN, Wang Q, Jiang R, Schultheiss TM (2006) Odd-skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells. Development 133:2995–3004
Zhang Z, Iglesias D, Eliopoulos N, El Kares R, Chu L, Romagnani P, Goodyer P (2011) A variant OSR1 allele which disturbs OSR1 mRNA expression in renal progenitor cells is associated with reduction of newborn kidney size and function. Hum Mol Genet 20:4167–4174
Mugford JW, Sipila P, McMahon JA, McMahon AP (2008) Osr1 expression demarcates a multi-potent population of intermediate mesoderm that undergoes progressive restriction to an Osr1-dependent nephron progenitor compartment within the mammalian kidney. Dev Biol 324:88–98
Armstrong JF, Pritchard-Jones K, Bickmore WA, Hastie ND, Bard JB (1993) The expression of the Wilms’ tumour gene, WT1, in the developing mammalian embryo. Mech Dev 40:85–97
Moore AW, McInnes L, Kreidberg J, Hastie ND, Schedl A (1999) YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis. Development 126:1845–1857
Challen GA, Martinez G, Davis MJ, Taylor DF, Crowe M, Teasdale RD, Grimmond SM, Little MH (2004) Identifying the molecular phenotype of renal progenitor cells. J Am Soc Nephrol 15:2344–2357
Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R (1993) WT-1 is required for early kidney development. Cell 74:679–691
Martinez-Estrada OM, Lettice LA, Essafi A, Guadix JA, Slight J, Velecela V, Hall E, Reichmann J, Devenney PS, Hohenstein P, Hosen N, Hill RE, Munoz-Chapuli R, Hastie ND (2010) Wt1 is required for cardiovascular progenitor cell formation through transcriptional control of Snail and E-cadherin. Nat Genet 42:89–93
Herzlinger D, Qiao J, Cohen D, Ramakrishna N, Brown AM (1994) Induction of kidney epithelial morphogenesis by cells expressing Wnt-1. Dev Biol 166:815–818
Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP (2005) Wnt9b plays a central role in the regulation of mesenchymal-to-epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell 9:283–292
Schmidt-Ott KM, Masckauchan TN, Chen X, Hirsh BJ, Sarkar A, Yang J, Paragas N, Wallace VA, Dufort D, Pavlidis P, Jagla B, Kitajewski J, Barasch J (2007) beta-catenin/TCF/Lef controls a differentiation-associated transcriptional program in renal epithelial progenitors. Development 134:3177–3190
Park JS, Valerius MT, McMahon AP (2007) Wnt/beta-catenin signaling regulates nephron induction during mouse kidney development. Development 134:2533–2539
Fukuzawa R, Heathcott RW, More HE, Reeve AE (2007) Sequential WT1 and CTNNB1 mutations and alterations of beta-catenin localisation in intralobar nephrogenic rests and associated Wilms tumours: two case studies. J Clin Pathol 60:1013–1016
Shi B, Liang J, Yang X, Wang Y, Zhao Y, Wu H, Sun L, Zhang Y, Chen Y, Li R, Zhang Y, Hong M, Shang Y (2007) Integration of estrogen and Wnt signaling circuits by the Polycomb group protein EZH2 in breast cancer cells. Mol Cell Biol 27:5105–5119
Bracken AP, Dietrich N, Pasini D, Hansen KH, Helin K (2006) Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions. Genes Dev 20:1123–1136
Metsuyanim S, Pode-Shakked N, Schmidt-Ott KM, Keshet G, Rechavi G, Blumental D, Dekel B (2008) Accumulation of malignant renal stem cells is associated with epigenetic changes in normal renal progenitor genes. Stem Cells 26:1808–1817
Zirn B, Hartmann O, Samans B, Krause M, Wittmann S, Mertens F, Graf N, Eilers M, Gessler M (2006) Expression profiling of Wilms tumors reveals new candidate genes for different clinical parameters. Int J Cancer 118:1954–1962
Wagener N, Holland D, Bulkescher J, Crnkovic-Mertens I, Hoppe-Seyler K, Zentgraf H, Pritsch M, Buse S, Pfitzenmaier J, Haferkamp A, Hohenfellner M, Hoppe-Seyler F (2008) The enhancer of zeste homolog 2 gene contributes to cell proliferation and apoptosis resistance in renal cell carcinoma cells. Int J Cancer 123:1545–1550
Bracken AP, Pasini D, Capra M, Prosperini E, Colli E, Helin K (2003) EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer. EMBO J 22:5323–5335
O’Carroll D, Erhardt S, Pagani M, Barton SC, Surani MA, Jenuwein T (2001) The Polycomb-group gene Ezh2 is required for early mouse development. Mol Cell Biol 21:4330–4336
Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F (2006) The Polycomb group protein EZH2 directly controls DNA methylation. Nature 439:871–874
Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P, Jones RS, Zhang Y (2002) Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 298:1039–1043
Ezhkova E, Pasolli HA, Parker JS, Stokes N, Su IH, Hannon G, Tarakhovsky A, Fuchs E (2009) Ezh2 orchestrates gene expression for the stepwise differentiation of tissue-specific stem cells. Cell 136:1122–1135
Bardot ES, Valdes VJ, Zhang J, Perdigoto CN, Nicolis S, Hearn SA, Silva JM, Ezhkova E (2013) Polycomb subunits Ezh1 and Ezh2 regulate the Merkel cell differentiation program in skin stem cells. EMBO J 32:1990–2000
Caretti G, Di Padova M, Micales B, Lyons GE, Sartorelli V (2004) The Polycomb Ezh2 methyltransferase regulates muscle gene expression and skeletal muscle differentiation. Genes Dev 18:2627–2638
Varambally S, Dhanasekaran SM, Zhou M, Barrette TR, Kumar-Sinha C, Sanda MG, Ghosh D, Pienta KJ, Sewalt RG, Otte AP, Rubin MA, Chinnaiyan AM (2002) The Polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419:624–629
Mugford JW, Yu J, Kobayashi A, McMahon AP (2009) High-resolution gene expression analysis of the developing mouse kidney defines novel cellular compartments within the nephron progenitor population. Dev Biol 333:312–323
Kobayashi A, Valerius MT, Mugford JW, Carroll TJ, Self M, Oliver G, McMahon AP (2008) Six2 defines and regulates a multipotent self-renewing nephron progenitor population throughout mammalian kidney development. Cell Stem Cell 3:169–181
Pelletier J, Bruening W, Kashtan CE, Mauer SM, Manivel JC, Striegel JE, Houghton DC, Junien C, Habib R, Fouser L, Fine RN, Silverman BL, Haber DA, Housman D (1991) Germline mutations in the Wilms’ tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell 67:437–447
Diep CQ, Ma D, Deo RC, Holm TM, Naylor RW, Arora N, Wingert RA, Bollig F, Djordjevic G, Lichman B, Zhu H, Ikenaga T, Ono F, Englert C, Cowan CA, Hukriede NA, Handin RI, Davidson AJ (2011) Identification of adult nephron progenitors capable of kidney regeneration in zebrafish. Nature 470:95–100
Sagrinati C, Netti GS, Mazzinghi B, Lazzeri E, Liotta F, Frosali F, Ronconi E, Meini C, Gacci M, Squecco R, Carini M, Gesualdo L, Francini F, Maggi E, Annunziato F, Lasagni L, Serio M, Romagnani S, Romagnani P (2006) Isolation and characterization of multipotent progenitor cells from the Bowman’s capsule of adult human kidneys. J Am Soc Nephrol 17:2443–2456
Lazzeri E, Crescioli C, Ronconi E, Mazzinghi B, Sagrinati C, Netti GS, Angelotti ML, Parente E, Ballerini L, Cosmi L, Maggi L, Gesualdo L, Rotondi M, Annunziato F, Maggi E, Lasagni L, Serio M, Romagnani S, Vannelli GB, Romagnani P (2007) Regenerative potential of embryonic renal multipotent progenitors in acute renal failure. J Am Soc Nephrol 18:3128–3138
Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, McMahon AP, Bonventre JV (2008) Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell 2:284–291
Angelotti ML, Ronconi E, Ballerini L, Peired A, Mazzinghi B, Sagrinati C, Parente E, Gacci M, Carini M, Rotondi M, Fogo AB, Lazzeri E, Lasagni L, Romagnani P (2012) Characterization of renal progenitors committed toward tubular lineage and their regenerative potential in renal tubular injury. Stem Cells 30:1714–1725
Syres K, Harrison F, Tadlock M, Jester JV, Simpson J, Roy S, Salomon DR, Cherqui S (2009) Successful treatment of the murine model of cystinosis using bone marrow cell transplantation. Blood 114:2542–2552
Iglesias DM, El-Kares R, Taranta A, Bellomo F, Emma F, Besouw M, Levtchenko E, Toelen J, van den Heuvel L, Chu L, Zhao J, Young YK, Eliopoulos N, Goodyer P (2012) Stem cell microvesicles transfer cystinosin to human cystinotic cells and reduce cystine accumulation in vitro. PloS One 7:e42840
Mae S, Shono A, Shiota F, Yasuno T, Kajiwara M, Gotoda-Nishimura N, Arai S, Sato-Otubo A, Toyoda T, Takahashi K, Nakayama N, Cowan CA, Aoi T, Ogawa S, McMahon AP, Yamanaka S, Osafune K (2013) Monitoring and robust induction of nephrogenic intermediate mesoderm from human pluripotent stem cells. Nat Commun 4:1367
Hendry CE, Vanslambrouck JM, Ineson J, Suhaimi N, Takasato M, Rae F, Little MH (2013) Direct transcriptional reprogramming of adult cells to embryonic nephron progenitors. J Am Soc Nephrol 24:1424–1434
Nishikawa M, Yanagawa N, Kojima N, Yuri S, Hauser PV, Jo OD, Yanagawa N (2012) Stepwise renal lineage differentiation of mouse embryonic stem cells tracing in vivo development. Biochem Biophys Res Commun 417:897–902
Kim D, Dressler GR (2005) Nephrogenic factors promote differentiation of mouse embryonic stem cells into renal epithelia. J Am Soc Nephrol 16:3527–3534
Lusis M, Li J, Ineson J, Christensen ME, Rice A, Little MH (2010) Isolation of clonogenic, long-term self renewing embryonic renal stem cells. Stem Cell Res 5:23–39
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Iglesias, D.M., Akpa, M.M. & Goodyer, P. Priming the renal progenitor cell. Pediatr Nephrol 29, 705–710 (2014). https://doi.org/10.1007/s00467-013-2685-3
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-013-2685-3