Project/Area Number |
17K13224
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Applied health science
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Research Institution | Kumamoto University (2018-2019) Nagasaki University (2017) |
Principal Investigator |
Fujimaki Shin 熊本大学, 発生医学研究所, 特別研究員(SPD・PD・RPD) (10795678)
|
Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | Notchシグナル / 骨格筋幹細胞 / Notch2 / 成熟筋線維 / サテライト細胞 / 自己複製 / Notch1 / 加齢 / 糖尿病 |
Outline of Final Research Achievements |
Resident muscle stem cells, called as satellite cells, contribute to the postnatal maintenance, growth, repair, and regeneration of skeletal muscle. Current study focused on Notch signaling, which is highly conserved and plays important roles in many biological events, as a molecular mechanism for regulating satellite cell function. Here, I generated satellite cell-specific Notch1 and Notch2-deleted mice and investigated the function of these genes during muscle differentiation. As a result, I clarified that Notch1 and Notch2 coordinately regulate satellite cell pool via maintaining quiescence, preventing differentiation, and promoting self-renewal. This study can provide useful evidences for developing countermeasures against muscle disorders, such as muscle dystrophies and sarcopenia.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、サテライト細胞特異的にNotch1およびNotch2を欠損させた遺伝子改変マウスを用いることで、Notch1およびNotch2遺伝子がサテライト細胞の運命決定を制御して骨格筋幹細胞プールを維持していることを明らかにした。本研究は世界で初めてサテライト細胞特異的Notch受容体欠損マウスを用いた研究であり、本知見によって骨格筋幹細胞の制御機構の解明が加速すると考えられる。さらに、本研究を応用することで、筋ジストロフィーやサルコペニアといった筋疾患の予防・治療法の開発につながることが期待される。
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