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

Shunsuke Tanigawa, Hidekazu Naganuma, Yusuke Kaku, Takumi Era, Tetsushi Sakuma, Takashi Yamamoto, Atsuhiro Taguchi, Ryuichi Nishinakamura

研究成果: Contribution to journalArticle査読

7 被引用数 (Scopus)

抄録

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. Nishinakamura and colleagues reveal that activin can maintain human iPSC-derived nephron progenitors with higher efficiency than BMP7. The expanded progenitors possess robust capacity for kidney tissue formation both in vitro and in vivo.

本文言語英語
ページ(範囲)322-337
ページ数16
ジャーナルStem Cell Reports
13
2
DOI
出版ステータス出版済み - 8 13 2019

All Science Journal Classification (ASJC) codes

  • 生化学
  • 遺伝学
  • 発生生物学
  • 細胞生物学

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