Analysis of human iPSC differentiation into definitive endoderm using CRISPR screening
| Project/Area Number |
17K20146
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| Research Category |
Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Biological Sciences
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| Research Institution | Kyoto University |
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Principal Investigator |
YUSA Kosuke 京都大学, ウイルス・再生医科学研究所, 教授 (00813180)
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| Project Period (FY) |
2018 – 2020
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥58,500,000 (Direct Cost: ¥45,000,000、Indirect Cost: ¥13,500,000)
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| Keywords | ヒトES細胞 / ヒトiPS細胞 / 分化 / 胚性内胚葉 / CRISPRスクリーニング / 多能性 / 未分化能 / 細胞分化 / 分化指向性 / 内胚葉 |
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| Outline of Final Research Achievements |
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.
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| Academic Significance and Societal Importance of the Research Achievements |
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。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Minimal genome-wide human CRISPR-Cas9 library.2021
Author(s)
Goncalves E, Thomas M, Behan FM, Picco G, Pacini C, Allen F, Vinceti A, Sharma M, Jackson DA, Price S, Beaver CM, Dovey O, Parry-Smith D, Iorio F, Parts L, Yusa K, Garnett MJ.
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Journal Title
Genome Biology
Volume: 22
Issue: 1
DOI
Description
印刷中
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] KAT7 is a genetic vulnerability of acute myeloid leukemias driven by MLL rearrangements2021
Author(s)
Au YZ, Gu M, De Braekeleer E, Gozdecka M, Aspris D, Tarumoto Y, Cooper J, Yu J, Ong SH, Chen X, Tzelepis K, Huntly BJP, Vassiliou G, Yusa K.
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Journal Title
Leukemia
Volume: 35
Issue: 4
Pages: 1012-1022
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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