Cell metabolism determines the megakaryocyte lineage fate of hematopoietic stem cells
| Project/Area Number |
18K08364
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54010:Hematology and medical oncology-related
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| Research Institution | Tokyo Women's Medical University (2019-2020)
Kumamoto University (2018) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
須田 年生 熊本大学, 国際先端医学研究機構, 卓越教授 (60118453)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 造血幹細胞 / ミトコンドリア / 巨核球 / 静止期 / 分化 / 代謝 / 細胞代謝 |
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| Outline of Final Research Achievements |
The production of platelets in the bone marrow requires the differentiation of megakaryocytes (Mk) from hematopoietic stem cells (HSCs). This project aimed to delineate how the cytokine Thrombopoietin(Thpo) regulates Mk differentiation potential of HSCs. We identified that Thpo stimulates mitochondria metabolism in HSCs which skewed HSCs towards Mk lineage differentiation. Furthermore, we analyzed Thpo knock out mice and identified that Thpo signaling was required for maintaining HSCs in a quiescent state. Our research highlights the significance of Thpo signaling in regulating HSC differentiation and maintenance through modifications of mitochondria metabolism.
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| Academic Significance and Societal Importance of the Research Achievements |
骨髄造血幹細胞の巨核球、血小板系統への分化バイアスメカニズムの詳細はわかっていない。本研究は、サイトカイン, Thrombopoietin(Thpo)によるミトコンドリアによるエネルギー代謝が造血幹細胞の巨核球分化に関与することを明確にした。生体外におけるHSCの増幅、分化は幹細胞を臨床治療に応用する際に重要であり、本研究はその手法の開発、改善のために役立つと思われる。また、造血幹細胞機能不全の起こる様々な血液疾患の病態解明、新規治療開発にも役立つと思われる。
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Report
(3 results)
Research Products
(9 results)
