Activin Is Superior to BMP7 for Efficient Maintenance of Human iPSC-Derived Nephron Progenitors

Publication date: Available online 1 August 2019Source: Stem Cell ReportsAuthor(s): Shunsuke Tanigawa, Hidekazu Naganuma, Yusuke Kaku, Takumi Era, Tetsushi Sakuma, Takashi Yamamoto, Atsuhiro Taguchi, Ryuichi NishinakamuraSummaryKidney formation is regulated by the balance between maintenance and differentiation of nephron progenitor cells (NPCs). Now that directed differentiation of NPCs from human induced pluripotent stem cells (iPSCs) can be achieved, maintenance and propagation of NPCs in vitro should be beneficial for regenerative medicine. Although WNT and FGF signals were previously shown to be essential for NPC propagation, the requirement for BMP/TGFβ signaling remains controversial. Here we reveal that activin has superior effects to BMP7 on maintenance efficiency of human iPSC-derived NPCs. Activin expanded ITGA8+/PDGFRA−/SIX2-GFP+ NPCs by 5-fold per week at 80%–90% efficiency, and the propagated cells possessed robust capacity for nephron formation both in vitro and in vivo. The expanded cells also maintained their nephron-forming potential after freezing. Furthermore, the protocol was applicable to multiple non-GFP-tagged iPSC lines. Thus, our activin-based protocol will be applicable to a variety of research fields including disease modeling and drug screening.Graphical Abstract
Source: Stem Cell Reports - Category: Stem Cells Source Type: research