| Project/Area Number |
26221309
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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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| Research Field |
Hematology
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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)
石津 綾子 熊本大学, 国際先端医学研究機構, 客員准教授 (10548548)
梅本 晃正 熊本大学, 国際先端医学研究機構, 特任助教 (50620225)
坂本 比呂志 熊本大学, 発生医学研究所, 助教 (00347014)
田久保 圭誉 慶應義塾大学, 医学部, 講師 (50502788)
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| Project Period (FY) |
2014-05-30 – 2019-03-31
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| Project Status |
Discontinued (Fiscal Year 2018)
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| Budget Amount *help |
¥195,000,000 (Direct Cost: ¥150,000,000、Indirect Cost: ¥45,000,000)
Fiscal Year 2018: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000)
Fiscal Year 2017: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000)
Fiscal Year 2016: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000)
Fiscal Year 2015: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000)
Fiscal Year 2014: ¥39,000,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥9,000,000)
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| Keywords | 造血幹細胞 / ニッチ / 細胞代謝 / 細胞回転 / 幹細胞ニッチ / 幹細胞老化 / 人工ニッチ / 幹細胞制御 / 巨核球 / 細胞周期 / 炎症性サイトカイン / 白血病幹細胞 |
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| Outline of Final Research Achievements |
It is suggested that hematopoietic stem cells (HSCs) show two types of cell division patterns; self-renewal cell division, which reproduces stem cells, and differentiation division, which generates functioning mature cells. Understanding for cell fate decision of HSCs is a long-standing subject in the research field of hematopoiesis, but it has not been realized yet. In this project, we have validated how mitochondrial function affects the cell division of HSCs. We have shown that oxidative metabolism is critical for the regulation of quiescence and maintenance of HSCs. More importantly, we clarified the underlying molecular mechanisms how mitochondria -lysosome metabolism regulates HSC and macrophage/osteoclast function through the analysis for folliculin (FLCN)-TFE3 axis. These results may be translated to the manipulation of HSCs and their progenies by the mitochondrial regulation.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、幹細胞研究は、再生医療などの応用において注目されるが、その実現化においても幹細胞の本質的な属性を知ることは重要と考える。本研究では、幹細胞の周囲にある細胞(ニッチ)の解析を進めると同時に、ミトコンドリア機能の制御ということに焦点を絞って、幹細胞の動態を明らかにした。本研究成果は、いくつかの論文(総説を含む)に発表し、高い評価を得ることができた。また、国際学会（EHA,ASHなど）で招待講演を行った。
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| Assessment Rating |
Verification Result (Rating)
A-
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Assessment Rating |
Result (Rating)
A: Progress in the research is steadily towards the initial goal. Expected research results are expected.
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