| Project/Area Number |
17K16200
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | National Center for Global Health and Medicine |
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Principal Investigator |
Kobayashi Hiroshi 国立研究開発法人国立国際医療研究センター, その他部局等, 研究員 (10749542)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 造血幹細胞 / ステムセルエイジング / 単一細胞RNAシークエンス / 加齢 |
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| Outline of Final Research Achievements |
The applicants obtained transcriptomes of 50-90 hematopoietic stem cells at various ages. Younger hematopoietic stem cells and aged hematopoietic stem cells formed distinct clusters in gene expression, but exhibited homogeneous cell populations within each group, suggesting that hematopoietic stem cells undergo uniform qualitative changes during the aging process.
Elevated expression of self-renewal genes and TPO-related genes were observed. In order to explore common mechanisms underlying the functional decline during aging and in vitro culture, the culture conditions were re-examined, and high lipid concentration, low cytokines, and hypoxia were found to be the minimum requirement for maintaining hematopoietic stem cells in a quiescent state.
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| Academic Significance and Societal Importance of the Research Achievements |
造血幹細胞は骨髄内において、静止期に維持されることを特徴としており、生涯に渡る造血能を維持する役割を担っている。造血幹細胞は長寿命であるものの、加齢に伴い造血再構築能および正常な分化能を徐々に失い、白血病などの造血器悪性腫瘍の発生母地となる。本研究によって造血幹細胞の細胞集団が単一細胞レベルで均質に変容していくこと、その分子メカニズムとして造血幹細胞の自己複製因子が関わっていることを明らかにした。さらに造血幹細胞を体外で生体内と同様に維持する培養法を見出したことで、今後の加齢造血幹細胞の研究や、加齢に関連する造血器疾患の治療薬の研究開発にも有用な方法論を報告できた。
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