| Project/Area Number |
17K19339
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Molecular and Genome biology and related fields
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Hisatake Koji 筑波大学, 医学医療系, 教授 (70271236)
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| Co-Investigator(Kenkyū-buntansha) |
西村 健 筑波大学, 医学医療系, 准教授 (80500610)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | iPS細胞 / リプログラミング / 代謝変換 / ミトコンドリア / 活性酸素 / 解糖系 / Tcl1 / 酸化的リン酸化 / ROS / MitoTracker / 再生医学 / DNA変異 |
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| Outline of Final Research Achievements |
In this project, we found that Tcl1 enhances the metabolic shift from mitochondrial respiration to glycolysis during iPSC generation and improves the efficiency of iPSC generation. In addition, iPSC promotes the metabolic shift at the late stage rather than the early stage of iPSC generation. Over-expression of exogenous Tcl1 during iPSC generation not only promotes the metabolic shift and increases the efficiency of iPSC generation, but also reduces the production of reactive oxygen species (ROS), which may damage the genome of the derived iPSCs. Our results raised the possibility that Tcl1 over-expression improves the quality of the derived iPSCs, probably via reduction of the DNA damages that occur during iPSC generation.
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| Academic Significance and Societal Importance of the Research Achievements |
iPS細胞誘導過程では、ミトコンドリアでの酸化的リン酸化が一過性に活性化され、それに伴って活性酸素（ROS）の産生量が増える。ROSはDNA損傷の原因の一つであるので、iPS細胞誘導時に発生するROSがDNA損傷を誘発し、それがiPS細胞におけるゲノム変異の一因となっている可能性がある。本研究では、Tcl1が酸化的リン酸化を抑制することに着目し、iPS細胞誘導過程でTcl1がミトコンドリア量と数、代謝及びROS産生に及ぼす影響を解析し、Tcl1がROS産生を低減することを明らかにした。この成果は、ゲノム変異の少ないiPS細胞作製へとつながり、iPS細胞の再生医療への実用化を加速させる。
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