| Project/Area Number |
18K15050
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Keio University |
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Principal Investigator |
Morita Yuika 慶應義塾大学, 医学部(信濃町), 研究員 (50783685)
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| Project Period (FY) |
2018-04-01 – 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 心筋分化 / 代謝 / 再生医療 / 心臓発生 / 心筋代謝 / ペースメーカー細胞 / 分化 / ES/iPS細胞 |
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| Outline of Final Research Achievements |
The purpose of this study is to understand the maturation and maintenance mechanisms of human pluripotent cell-derived cardiomyocytes (hPSC-CM) by the use of knowledge of region-specific metabolites using mouse heart tissue. After I qualified the metabolites of adult mouse heart tissue with IMAGING-MS system which able to measure metabolites as exact as possible, I found that there were huge differences between atria and ventricle in vivo. To reveal whether these metabolic differences influence on the survival and functional maintenance of atria and ventricular cardiomyocytes, I established atrial cardiomyocytes differentiation method from human pluripotent stem cells (hPSCs) because I should have utilized high purity of cardiomyocytes, and then I compared characteristics between hPSC-derived atria and ventricular cardiomyocytes by multi-omics system. These analyses revealed that hPSC-derived atria cardiomyocytes are more hyperenergetic than PSC-derived ventricular cardiomyocytes.
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| Academic Significance and Societal Importance of the Research Achievements |
代謝はエピゲノム環境を変化させ遺伝子発現を制御することが報告されているが、ヒト多能性幹細胞由来の心房筋と心室筋の代謝相違は明らかにされておらず、代謝相違が生存や機能維持に関わっていることも不明である。本研究は代謝が細胞に及ぼす影響を解明する重要性を示しており、学術的意義は大きい。また、各心筋の正常な代謝を理解することで、今後ヒト多能性幹細胞由来の心筋を移植する際にも正常な心筋を代謝の観点から判別できる他、疾患ヒト多能性幹細胞由来の心筋との代謝比較により疾患原因を解明する手掛かりになる可能性もあり、再生医療や薬剤応答評価に繋げることができ社会的意義も大きい。
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