| Project/Area Number |
25860732
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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 |
Neurology
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| Research Institution | National Center of Neurology and Psychiatry |
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Principal Investigator |
Yokota Mutsumi 国立研究開発法人国立精神・神経医療研究センター, 神経研究所疾病研究第二部, 科研費研究員 (10647415)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | m.3243A>G / ミトコンドリア機能異常 / iPS細胞 / 細胞初期化 / 分化 / 神経細胞 / 心筋細胞 / m.3243A>G変異 / 神経系細胞 / 心血管系細胞 / 造血系細胞 / ミトコンドリア病 |
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| Outline of Final Research Achievements |
I focused on the effects of mitochondrial respiratory dysfunction caused by m.3243A>G heteroplasmy in MT-TL1 gene on cellular reprogramming and differentiation. I found that generation of iPSCs was drastically depressed only by high proportions of m.3243A>G, and these proportions were strongly associated with the degree of induced mitochondrial respiratory dysfunction. Furthermore, I found that patient-derived iPSC lines carrying quite high proportions of m.3243A>G showed both induced neuronal cell death and inhibited cardiac lineage-commitment. Therefore, these findings clearly demonstrate that mitochondrial respiratory dysfunction constitutes a roadblock to cellular reprogramming and inhibits maturation and survival of iPSC-derived neurons and cardiomyocytes. This study also suggests that physiological integrity of mitochondria must be a key factor in cellular fate-determination processes, including reprogramming and differentiation.
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