2021 Fiscal Year Final Research Report
Elucidation of the integrin-dependent signaling pathway in hematopoietic stem cell development.
Project/Area Number |
19K06438
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 42030:Animal life science-related
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Research Institution | Kanazawa University |
Principal Investigator |
Kobayashi Isao 金沢大学, 生命理工学系, 准教授 (30774757)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 造血幹細胞 / ゼブラフィッシュ / 分化 / シグナル伝達 |
Outline of Final Research Achievements |
During embryonic development, hematopoietic stem cells (HSCs) are formed from angioblasts, which are common progenitors of vascular endothelial cells. However, the detailed molecular mechanism of their fate determination has remained unclear. In this study, we investigated the role of integrin signaling pathways in angioblasts using zebrafish, and found that a small GTPase, RhoH, is essential for HSC formation. Furthermore, we revealed a novel molecular mechanism by which RhoH promotes HSC formation via suppressing Zap70. The signaling pathway of integrin-RhoH revealed in this study may play an important role in HSC formation.
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Free Research Field |
発生生物学
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Academic Significance and Societal Importance of the Research Achievements |
造血幹細胞をヒトiPS細胞から分化誘導することができれば、骨髄移植の代替法となるが、未だにiPS細胞から造血幹細胞への分化誘導は困難である。iPS細胞は初期胚の多能性細胞と類似の特徴を持つことから、胚発生期における造血幹細胞の形成過程を生体外で模倣できれば、iPS細胞から造血幹細胞を誘導することが可能になると考えられている。本研究で見出したRhoHは造血幹細胞の形成に重要な分子であることから、今後iPS細胞へ応用することで、造血幹細胞の分化誘導法の確立に貢献できる可能性がある。
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