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

Stem Cell Reports
Shunsuke TanigawaRyuichi Nishinakamura

Abstract

Kidney 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.

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Citations

Dec 8, 2019·Nature Reviews. Nephrology·Melissa H Little, Kynan T Lawlor
Apr 9, 2020·Frontiers in Cell and Developmental Biology·Niloofar Khoshdel RadReza Moghadasali
Feb 19, 2021·Scientific Reports·Tomoko OhmoriRyuichi Nishinakamura
Feb 12, 2021·Development, Growth & Differentiation·Tatsuya ShimizuKenji Osafune
Mar 3, 2020·Biochemical and Biophysical Research Communications·Hiraku TsujimotoKenji Osafune
Jun 3, 2021·Cells·Michael NamestnikovBenjamin Dekel

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Methods Mentioned

BETA
PCR
Flow-cytometry
RNA-seq
flow cytometry

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