| Project/Area Number |
20K22615
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0701:Biology at molecular to cellular levels, and related fields
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| Research Institution | Tohoku University |
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Principal Investigator |
Shibata Shun 東北大学, 医学系研究科, 助教 (40885670)
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | ヒトＴＳ細胞 / Hippo-YAPシグナル / ヒトTS細胞 / ES細胞 / TS細胞 / 胚体外系譜 |
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| Outline of Research at the Start |
本研究では、当研究室樹立のヒトTS細胞とES細胞からTS細胞に分化転換したモデル細胞（ES-TS細胞）を用い、ヒト特異的なHippo-YAPシグナルの細胞系譜決定における役割について検討する。これらの成果より、マウスの胚体外細胞系譜決定機構との相違点を明らかにし、胎盤発生におけるヒト特異性と保存性について検討する。
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| Outline of Final Research Achievements |
We investigated the involvement of Hippo-YAP signaling in the fate determination and maintenance of extraembryonic lineages using human stem cell lines. Immunostaining results showed that YAP localized in the nucleus and cytoplasm in human naive ES cells. In human TS cells, YAP was predominantly localized in the nucleus. We also analyzed localization of YAP during ES-TS cell trans-differentiation. Decreased expression of OCT4 and nuclear translocation of YAP were confirmed over time. Moreover, the nuclear translocation of YAP was prominent in GATA3, a maker of trophoblast lineage, -positive cells. Furthermore, YAP-TEAD inhibitor verteporfin inhibited cell proliferation of human TS cells in a concentration-dependent manner. These results suggest the involvement of YAP in the differentiation of human ES cells into extraembryonic lineage and the maintenance of TS cells.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒト受精卵から内部細胞塊（ICM）と栄養外胚葉（TE）に細胞系譜は分離し、胚盤胞が形成される。マウスの場合、ICMとTEの運命決定にHippo-YAPシグナルが関与することが知られる。しかしヒトの場合、Hippo-YAPシグナルの関与を含め、ICMとTEの運命決定機構の詳細は明らかでない部分が多い。本研究では、ヒト胚性幹（ES）細胞や栄養膜幹（TS）細胞等を活用し、運命決定機構や栄養膜系譜維持へのHippo-YAPシグナルの関与を示した。本研究成果は、ヒト初期発生機構の分子機序の理解の一助となり得ると期待する。
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