Research Project
Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
It has been known that there is substantial heterogeneity of differentiation preference among human pluripotent stem cell (hPSC) lines. Highly efficient differentiation is prerequisite for the usage of hPSCs in various applications such as in vitro disease modeling and cell-based therapy; however, the heterogeneity can limit the potential of hPSC lines. The current study aimed to address this issue by identifying factors that affect hPSC differentiation, particularly into definitive endoderm (DE). We conducted CRISPR screening and identified several differentiation blocker candidates. Genetic inactivation of these factors increased DE differentiation in multiple hPSC lines. The molecular basis of this effect remains elusive, but our findings may generate an efficient differentiation protocol applicable for a wide range of hPSC lines.
これまでに複数の大型プロジェクトによって正常および患者由来ヒトiPS細胞が作製されている。またヒトES細胞株も多数存在する。このようなヒト多能性幹細胞の応用例として、培養容器上で細胞分化を行って病気を再現し、メカニズム解明や治療法探索があげられる。しかし、提供者が異なるiPS細胞は分化効率の差が大きく、応用研究の障壁となっている。本研究は、この障壁の原因となる候補因子をゲノム編集技術を用いた遺伝子スクリーニングによって同定した。より効率が良く高品質な分化細胞を得るための分化法の開発につながり、今後のヒト多能性幹細胞を用いた研究への応用が期待される。
All 2021 2019 2018 Other
All Int'l Joint Research (1 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results, Peer Reviewed: 2 results, Open Access: 2 results) Presentation (11 results) (of which Int'l Joint Research: 4 results, Invited: 11 results)
Genome Biology
Volume: 22 Issue: 1
10.1186/s13059-021-02268-4
Leukemia
Volume: 35 Issue: 4 Pages: 1012-1022
10.1038/s41375-020-1001-z
120006976051
