2020 Fiscal Year Final Research Report
Establishing early embryonic development using naive pluripotent stem cells
| Project/Area Number |
16H02465
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2021-03-31
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| Keywords | 発生分化 / 幹細胞 |
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| Outline of Final Research Achievements |
Using naive human pluripotent stem cells (PSCs), we established a differentiation model from pre-implantation trophectoderm to syncytiotrophoblast and extravillous trophoblast via post-implantation cytotrophoblast (CT). In addition, we established a culture method to induce hypoblast and produced bilaminar disk-like structures (bilaminiods) by co-culturing human pre-implantation epiblast and our naive PSC-derived hypoblast. Hypoblast generated the basement membrane and polarity of epiblast, the pro-amniotic cavity, and the anterior-posterior axis. Epiblast started to express primitive streak genes. These observations all suggest we could model the pre-implantation to post-implantation transition of the human embryo in vitro.
Finally, we succeeded in establishing new primed and naive marmoset PSCs, finding some signaling pathways were conserved in humans and marmosets. This result emphasizes the importance of using monkey embryo data when evaluating human PSCs.
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| Free Research Field |
発生分化
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| Academic Significance and Societal Importance of the Research Achievements |
着床期の初期発生は、ヒト・非ヒト霊長類では不明な点が多く、マウスとも異なる。しかし、霊長類胚を用いた研究は、倫理面に対する問題を含み困難である。自身が報告したnaive型ヒト多能性幹細胞を用いて世界で初めて、栄養外胚葉から始まる胎盤細胞の分化モデルや二層性胚盤様構造(Bilaminoids)モデルを樹立した。ブラックボックスであったヒト初期発生を明らかにすることができ、今後幹細胞を用いたヒト初期発生研究分野を作りだす成果である。マーモセット胚を利用することで、非ヒト霊長類を用いた初期発生研究の基盤構築に成功した。霊長類研究の重要性を示すとともに不妊・発生異常にも貢献する意義が高い成果である。
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