title: In Vitro Propagation and Branching Morphogenesis from Single Ureteric Bud Cells.
abstract: A method to maintain and rebuild ureteric bud (UB)-like structures from UB cells in vitro could provide a useful tool for kidney regeneration. We aimed in our present study to establish a serum-free culture system that enables the expansion of UB progenitor cells, i.e., UB tip cells, and reconstruction of UB-like structures. We found that fibroblast growth factors or retinoic acid (RA) was sufficient for the survival of UB cells in serum-free condition, while the proliferation and maintenance of UB tip cells required glial cell-derived neurotrophic factor together with signaling from either WNT-β-catenin pathway or RA. The activation of WNT-β-catenin signaling in UB cells by endogenous WNT proteins required R-spondins. Together with Rho kinase inhibitor, our culture system facilitated the expansion of UB tip cells to form UB-like structures from dispersed single cells. The UB-like structures thus formed retained the original UB characteristics and integrated into the native embryonic kidneys.
authors.affiliation: Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA 91343, USA; Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA. Electronic address: shunsukeyuri@ucla.edu.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Yuri
authors.affiliation: Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA 91343, USA; Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA 91343, USA; Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Yanagawa
authors.affiliation: Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA 91343, USA; Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Oak D
authors.initials: OD
authors.lastname: Jo
authors.affiliation: Medical and Research Services, Greater Los Angeles Veterans Affairs Healthcare System at Sepulveda, North Hills, CA 91343, USA; Department of Medicine, University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, CA 90095, USA. Electronic address: nori@ucla.edu.
authors.forename: Norimoto
authors.initials: N
authors.lastname: Yanagawa
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D005346:Fibroblast Growth Factors / Q000378:metabolism; D007668:Kidney / Q000166:cytology* / Q000196:embryology*; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D019699:Thrombospondins / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D019699:Thrombospondins; D014212:Tretinoin; D005346:Fibroblast Growth Factors
keywords: R-spondin; branching morphogenesis; fibroblast growth factor; kidney progenitor cells; retinoic acid; ureteric bud