Escape from Pluripotency via Inhibition of TGF-β/BMP and Activation of Wnt Signaling Accelerates Differentiation and Aging in hPSC Progeny Cells

Koki Fujimori, Takuya Matsumoto, Fumihiko Kisa, Nobutaka Hattori, Hideyuki Okano, Wado Akamatsu

研究成果: Article査読

39 被引用数 (Scopus)

抄録

Human pluripotent stem cells (hPSCs) represent a potentially valuable cell source for applications in cell replacement therapy, drug development, and disease modeling. For all these uses, it is necessary to develop reproducible and robust protocols for differentiation into desired cell types. However, differentiation protocols remain unstable and inefficient, which makes minimizing the differentiation variance among hPSC lines and obtaining purified terminally differentiated cells extremely time consuming. Here, we report a simple treatment with three small molecules—SB431542, dorsomorphine, and CHIR99021—that enhanced hPSC differentiation into three germ layers with a chemically transitional embryoid-body-like state (CTraS). Induction of CTraS reduced the innate differentiation propensities of hPSCs (even unfavorably differentiated hPSCs) and shifted their differentiation into terminally differentiated cells, particularly neurons. In addition, CTraS induction accelerated in vitro pathological expression concurrently with neural maturation. Thus, CTraS can promote the latent potential of hPSCs for differentiation and potentially expand the utility and applicability of hPSCs. Simple treatment with three small molecules enhanced hPSC differentiation into three germ layers, namely CTraS. CTraS reduced the innate differentiation propensities of hPSCs and shifted them into terminal differentiations. CTraS induction accelerated in vitro pathological expression with maturation and aging. Thus, CTraS can bring out the latent potential of hPSCs.

本文言語English
ページ(範囲)1675-1691
ページ数17
ジャーナルStem cell reports
9
5
DOI
出版ステータスPublished - 2017 11月 14

ASJC Scopus subject areas

  • 生化学
  • 遺伝学
  • 発生生物学
  • 細胞生物学

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