| Project/Area Number |
15K14430
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical genome science
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| Research Institution | The University of Kitakyushu |
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Principal Investigator |
HIDAKA KYOKO 北九州市立大学, 基盤教育センター, 教授 (00216681)
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| Research Collaborator |
NAKATSU yoshimichi
HIDAKA masumi
HAYASHIDA genki
OHNO mizuki
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | iPS細胞 / DNA修復 / ミスマッチ修復 / ミューテーター / 多能性幹細胞 / MSH2 / 細胞死誘導 / ゲノム編集 / 幹細胞 |
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| Outline of Final Research Achievements |
The genome of pluripotent stem cells (such as human iPS cells) has a low mutation rate and is very stable. It is important to know how the genome is stably maintained, on the other hand, the development of a system that can easily detect mutations is useful. This study focuses on mismatch repair (MMR) proteins. First, we clarified the relationship between DNA repair and cell death induction by MMR proteins in human cultured cells. Next, we established human iPS cells with MMR deficiency by genome editing technology and confirmed that this became a mutator with elevated spontaneous mutation rates. Our new findings may lead to the elucidation of the genome maintenance mechanism of pluripotent stem cells and the establishment of a highly sensitive mutation detection method.
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| Academic Significance and Societal Importance of the Research Achievements |
iPS細胞などの多能性幹細胞は再生医療の細胞ソースとして期待されているが、わずかでも変異が生じるとがん化につながるため、その遺伝情報（ゲノム）をできるだけ安定に保つことが重要である。一方、ゲノムが安定であればあるほどその変異を検出することが難しくなる。本研究では、DNA修復タンパク質の遺伝子をゲノム編集により操作することにより、通常よりも変異が起こる率が高くなるような株（ミューテーター株）を作成することができた。このような株を利用することで、iPS細胞のより安全な培養法の開発につながると期待できる。
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