{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T05:00:53Z","timestamp":1784091653022,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T00:00:00Z","timestamp":1580428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Generation of kidney organoids from pluripotent stem cells (PSCs) is regarded as a potentially powerful way to study kidney development, disease, and regeneration. Direct differentiation of PSCs towards renal lineages is well studied; however, most of the studies relate to generation of nephron progenitor population from PSCs. Until now, differentiation of PSCs into ureteric bud (UB) progenitor cells has had limited success. Here, we describe a simple, efficient, and reproducible protocol to direct differentiation of mouse embryonic stem cells (mESCs) into UB progenitor cells. The mESC-derived UB cells were able to induce nephrogenesis when co-cultured with primary metanephric mesenchyme (pMM). In generated kidney organoids, the embryonic pMM developed nephron structures, and the mESC-derived UB cells formed numerous collecting ducts connected with the nephron tubules. Altogether, our study established an uncomplicated and reproducible platform to generate ureteric bud progenitors from mouse embryonic stem cells.<\/jats:p>","DOI":"10.3390\/cells9020329","type":"journal-article","created":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T05:55:46Z","timestamp":1580450146000},"page":"329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mouse Embryonic Stem Cell-Derived Ureteric Bud Progenitors Induce Nephrogenesis"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2894-0905","authenticated-orcid":false,"given":"Zenglai","family":"Tan","sequence":"first","affiliation":[{"name":"Center for Cell Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Laboratory of Developmental Biology, Infotech Oulu, University of Oulu, Aapistie 5A, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Rak-Raszewska","sequence":"additional","affiliation":[{"name":"Center for Cell Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Laboratory of Developmental Biology, Infotech Oulu, University of Oulu, Aapistie 5A, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1182-1130","authenticated-orcid":false,"given":"Ilya","family":"Skovorodkin","sequence":"additional","affiliation":[{"name":"Center for Cell Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Laboratory of Developmental Biology, Infotech Oulu, University of Oulu, Aapistie 5A, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9319-3566","authenticated-orcid":false,"given":"Seppo J.","family":"Vainio","sequence":"additional","affiliation":[{"name":"Center for Cell Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Laboratory of Developmental Biology, Infotech Oulu, University of Oulu, Aapistie 5A, 90220 Oulu, Finland"},{"name":"Borealis Biobank of Northern Finland, Oulu Central Hospital, 90220 Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nature10761","article-title":"The promise of induced pluripotent stem cells in research and therapy","volume":"481","author":"Robinton","year":"2012","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/nature15695","article-title":"Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis","volume":"526","author":"Takasato","year":"2015","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8715","DOI":"10.1038\/ncomms9715","article-title":"Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids","volume":"6","author":"Freedman","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1038\/nbt.3392","article-title":"Nephron organoids derived from human pluripotent stem cells model kidney development and injury","volume":"33","author":"Morizane","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1016\/j.kint.2018.05.003","article-title":"A CRISP(e)R view on kidney organoids allows generation of an induced pluripotent stem cell\u2013derived kidney model for drug discovery","volume":"94","author":"Jonebring","year":"2018","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"649","DOI":"10.3904\/kjim.2018.198","article-title":"Applications of kidney organoids derived from human pluripotent stem cells","volume":"33","author":"Kim","year":"2018","journal-title":"Korean J. Intern. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-07594-z","article-title":"3D organoid-derived human glomeruli for personalised podocyte disease modelling and drug screening","volume":"9","author":"Hale","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.stem.2017.10.011","article-title":"Higher-Order Kidney Organogenesis from Pluripotent Stem Cells","volume":"21","author":"Taguchi","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/j.stem.2018.04.022","article-title":"High-Throughput Screening Enhances Kidney Organoid Differentiation from Human Pluripotent Stem Cells and Enables Automated Multidimensional Phenotyping","volume":"22","author":"Czerniecki","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nmat4994","article-title":"Organoid cystogenesis reveals a critical role of microenvironment in human polycystic kidney disease","volume":"16","author":"Cruz","year":"2017","journal-title":"Nat. Mater."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Araoka, T., Mae, S., Kurose, Y., Uesugi, M., Ohta, A., Yamanaka, S., and Osafune, K. (2014). Efficient and Rapid Induction of Human iPSCs\/ESCs into Nephrogenic Intermediate Mesoderm Using Small Molecule-Based Differentiation Methods. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0084881"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/ncb2894","article-title":"Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney","volume":"16","author":"Takasato","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.stem.2013.11.010","article-title":"Redefining the in vivo origin of metanephric nephron progenitors enables generation of complex kidney structures from pluripotent stem cells","volume":"14","author":"Taguchi","year":"2014","journal-title":"Cell Stem Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41563-019-0287-6","article-title":"Fine tuning the extracellular environment accelerates the derivation of kidney organoids from human pluripotent stem cells","volume":"18","author":"Garreta","year":"2019","journal-title":"Nat. Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41592-019-0325-y","article-title":"Flow-enhanced vascularization and maturation of kidney organoids in vitro","volume":"16","author":"Homan","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41581-019-0130-y","article-title":"Fluid flow enhances vascularization and maturation of kidney organoids","volume":"15","author":"Allison","year":"2019","journal-title":"Nat. Reviews. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.stem.2019.06.009","article-title":"Generation of Human PSC-Derived Kidney Organoids with Patterned Nephron Segments and a De Novo Vascular Network","volume":"25","author":"Low","year":"2019","journal-title":"Cell Stem Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.stemcr.2018.06.018","article-title":"A Simple Bioreactor-Based Method to Generate Kidney Organoids from Pluripotent Stem Cells","volume":"11","author":"Przepiorski","year":"2018","journal-title":"Stem Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1038\/ncb2872","article-title":"Directed differentiation of human pluripotent cells to ureteric bud kidney progenitor-like cells","volume":"15","author":"Xia","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16964","DOI":"10.1074\/jbc.M115.662635","article-title":"Severe Extracellular Matrix Abnormalities and Chondrodysplasia in Mice Lacking Collagen Prolyl 4-Hydroxylase Isoenzyme II in Combination with a Reduced Amount of Isoenzyme I","volume":"290","author":"Aro","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1681\/ASN.2013060584","article-title":"Functional genetic targeting of embryonic kidney progenitor cells ex vivo","volume":"26","author":"Junttila","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-1-4939-9021-4_4","article-title":"Experimental Tubulogenesis Induction Model in the Mouse","volume":"Volume 1926","author":"Vainio","year":"2019","journal-title":"Kidney Organogenesis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"83","DOI":"10.4161\/org.7.2.14881","article-title":"An improved kidney dissociation and reaggregation culture system results in nephrons arranged organotypically around a single collecting duct system","volume":"7","author":"Ganeva","year":"2011","journal-title":"Organogenesis"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1681\/ASN.2012121143","article-title":"Direct Transcriptional Reprogramming of Adult Cells to Embryonic Nephron Progenitors","volume":"24","author":"Hendry","year":"2013","journal-title":"J. Am. Soc. Nephrol. Jasn."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.scr.2010.03.003","article-title":"Isolation of clonogenic, long-term self renewing embryonic renal stem cells","volume":"5","author":"Lusis","year":"2010","journal-title":"Stem Cell Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/BF00849241","article-title":"Early organogenesis of the kidney","volume":"1","author":"Sariola","year":"1987","journal-title":"Pediatr. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ki.2009.482","article-title":"Dissociation of embryonic kidneys followed by reaggregation allows the formation of renal tissues","volume":"77","author":"Unbekandt","year":"2010","journal-title":"Kidney Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"H893","DOI":"10.1152\/ajpheart.01038.2008","article-title":"Inhibition of Rho-dependent kinases ROCK I\/II activates VEGF-driven retinal neovascularization and sprouting angiogenesis","volume":"296","author":"Kroll","year":"2009","journal-title":"Am. J. Physiol.\u2014Heart Circ. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ydbio.2009.05.578","article-title":"Analysis of early nephron patterning reveals a role for distal RV proliferation in fusion to the ureteric tip via a cap mesenchyme-derived connecting segment","volume":"332","author":"Georgas","year":"2009","journal-title":"Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0070-2153(10)90005-7","article-title":"Kidney development: Two tales of tubulogenesis","volume":"90","author":"Little","year":"2010","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1242\/dev.02773","article-title":"Notch2, but not Notch1, is required for proximal fate acquisition in the mammalian nephron","volume":"134","author":"Cheng","year":"2007","journal-title":"Development"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5031","DOI":"10.1242\/dev.00697","article-title":"Gamma-secretase activity is dispensable for mesenchyme-to-epithelium transition but required for podocyte and proximal tubule formation in developing mouse kidney","volume":"130","author":"Cheng","year":"2003","journal-title":"Development"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1001\/jama.294.7.813","article-title":"Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators, for the Acute Renal Failure in Critically Ill Patients: A Multinational, Multicenter Study","volume":"294","author":"Uchino","year":"2005","journal-title":"JAMA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"899","DOI":"10.3109\/08860229609047716","article-title":"The Relationship Between Enzymuria and Kidney Enzyme Activities in Experimental Gentamicin Nephrotoxicity","volume":"18","author":"Whiting","year":"1996","journal-title":"Ren. Fail."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s002800000145","article-title":"The role of caspase family protease, caspase-3 on cisplatin-induced apoptosis in cisplatin-resistant A431 cell line","volume":"46","author":"Mese","year":"2000","journal-title":"Cancer Chemother. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ydbio.2016.08.024","article-title":"A strategy for generating kidney organoids: Recapitulating the development in human pluripotent stem cells","volume":"420","author":"Takasato","year":"2016","journal-title":"Dev. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.bbrc.2017.11.105","article-title":"Generation of branching ureteric bud tissues from human pluripotent stem cells","volume":"495","author":"Mae","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.kint.2016.02.021","article-title":"CD146+ cells are essential for kidney vasculature development","volume":"90","author":"Halt","year":"2016","journal-title":"Kidney Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/S0960-9822(02)00694-2","article-title":"Endothelial Signaling in Kidney Morphogenesis: A Role for Hemodynamic Forces","volume":"12","author":"Serluca","year":"2002","journal-title":"Curr. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1038\/s41586-018-0858-8","article-title":"Human blood vessel organoids as a model of diabetic vasculopathy","volume":"565","author":"Wimmer","year":"2019","journal-title":"Nature"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/2\/329\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:23Z","timestamp":1760172803000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/9\/2\/329"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,31]]},"references-count":40,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2020,2]]}},"alternative-id":["cells9020329"],"URL":"https:\/\/doi.org\/10.3390\/cells9020329","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737331191.793573123","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,31]]}}}