| Project/Area Number |
18H05284
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| Research Category |
Grant-in-Aid for Scientific Research (S)
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| Allocation Type | Single-year Grants |
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| Review Section |
Broad Section I
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| Research Institution | Kumamoto University |
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Principal Investigator |
SUDA Toshio 熊本大学, 国際先端医学研究機構, 卓越教授 (60118453)
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| Co-Investigator(Kenkyū-buntansha) |
馬場 理也 熊本大学, 国際先端医学研究機構, 准教授 (10347304)
梅本 晃正 熊本大学, 国際先端医学研究機構, 特任准教授 (50620225)
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| Project Period (FY) |
2018-06-11 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥182,000,000 (Direct Cost: ¥140,000,000、Indirect Cost: ¥42,000,000)
Fiscal Year 2022: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
Fiscal Year 2021: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
Fiscal Year 2020: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
Fiscal Year 2019: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
Fiscal Year 2018: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
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| Keywords | 造血幹細胞 / 造血微小環境（ニッチ) / 不均等分裂 / 自己複製 / ミトコンドリア / 造血微小循環（ニッチ) / 造血微小環境（ニッチ） / 造血微小環境(ニッチ) |
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| Outline of Final Research Achievements |
Functioning blood cells are supplied through the differentiation and proliferation of hematopoietic stem cells(HSCｓ). In normal hematopoiesis, bone marrow HSCs maintain their self-renewal capacity and remain in a quiescent state, prepared for stress hematopoiesis.
In this study, we elucidated the molecular mechanism of how thrombopoietin(Thpo) signaling works in the production of stem cells and megakaryocytes, regulates mitochondrial and endoplasmic reticulum(ER)metabolism and is involved in the differentiation and maintenance of HSCs. Furthermore, using Folliculin(Flcn) knockout mice, a tumor suppressor gene, we have clarified the critical role of mitochondrial metabolism and lysosome function in HSCs.
In fetal liver, we have shown that HSCs exclusively self-renew and do not contribute to differentiation, whereas mature cells are supplied from progenitor cells, indicating the in vitro amplification of HSCs by selective induction of self-renewal division of HSCs (Nature, 2022).
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| Academic Significance and Societal Importance of the Research Achievements |
胎児肝においては、造血幹細胞と前駆細胞(EMP)の2つの分化段階の細胞系譜は分離され、HSCは、もっぱら自己複製をし、分化には寄与しない、一方、成熟細胞は、前駆細胞から供給されるということを、造血幹細胞特異的に発現する遺伝子Hepatic Leukemic Factor, Hlfレポーターマウスを作製して明らかにした。まこれらのデータは、「幹細胞の自己複製と分化は切り離され得る」というきわめて重要なコンセプトと考えている(Nature, 2022)。 このことにより、幹細胞に胎児肝と同様の自己複製条件を与えれば、幹細胞だけを増幅させることも可能と考えられる。
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| Assessment Rating |
Ex-post Assessment Comments (Rating)
A+: In light of the aim of introducing the research area into the research categories, more research outcomes have been produced than expected.
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Assessment Rating |
Interim Assessment Comments (Rating)
A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.
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