2019 Fiscal Year Final Research Report
Function of Foxp2 in the maintenance of hematopoietic stem cells.
| Project/Area Number |
17K09907
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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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| Research Field |
Hematology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
新井 文用 九州大学, 医学研究院, 教授 (90365403)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 造血幹細胞 / 細胞周期 / Foxp2 |
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| Outline of Final Research Achievements |
This study found that Foxp2 was specifically expressed in quiescent hematopoietic stem cells (HSCs), and suggested that Foxp2 negatively regulates the cell cycle of HSCs. Foxp2-deficient mouse-derived HSCs were found to have activation of the cell cycle, activation of several signal pathways observed during proliferation, and enhancement of energy production. On the other hand, HSCs exogenously overexpressing Foxp2 were found to highly express CDK inhibitors and suppress the signal system that promotes proliferation. It was also shown that these cells can withstand the stress of transplantation and maintain long-term bone marrow reconstitution ability.
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| Free Research Field |
幹細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
造血幹細胞が生体において長期に渡って維持されるためには、細胞周期を低速に抑えることが必須であるが、これまでどのようなシグナル系を介して静止期に維持されるのかは不明であった。そこで本研究では、静止期造血幹細胞に特異的なFoxp2を介した維持機構について解析を行い、Foxp2が影響を与えるいくつかのシグナル経路を見出すことができた。さらに、造血幹細胞に対して外因性にFoxp2の発現を高めることで静止期の維持を促進し、幹細胞の活性自体も長期に保持できることが分かった。本研究成果は、幹細胞制御技術の開発において重要な知見となることが考えられ、生体外でのヒト造血幹細胞の遺伝子治療への応用が期待される。
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