| Project/Area Number |
15K01280
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Biomedical engineering/Biomaterial science and engineering
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Research Collaborator |
Yue Fengming
Sasaki Katsunori
Hirashima Kanji
Fujii Masako
Nakamura Shunsuke
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 多能性幹細胞 / iPS細胞 / 未分化維持 / ヒト多能性幹細胞 / ヒトiPS細胞 / エピジェネティック / ポリコーム / ポリコーム遺伝子群 / 未分化状態 |
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| Outline of Final Research Achievements |
Maintenance of undifferentiated state is a critical requirement for regenerative medicine using pluripotent stem cells. In this study, we created the spontaneous differentiation by removing MEF cells, and then analyzed global changes of gene expression during the spontaneous differentiation using DNA microarray. As results of the microarray analysis using four human pluripotent stem cell lines, we found that some polycomb group genes were commonly up- regulated during the collapse of undifferentiated state. Then we analyzed function of the spontaneous differentiation-induced polycomb group genes in pluripotent stem cells by CRISPR-Cas9 mediated knockout. These knockout cells showed tendency to differentiate more frequently than control. Therefore these polycomb group proteins may function as defense against the spontaneous differentiation. To evaluate the proposed function, we analyzed cell lines over-expressing the polycomb genes. The results supported the hypothesis.
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| Academic Significance and Societal Importance of the Research Achievements |
ヒトiPS細胞などの多能性幹細胞は、様々な細胞に分化する能力を持つため、疾患のある組織を健康な組織で置き換える再生医療において、その細胞供給源になると期待されている。多分化能を保持するためには、未だ分化してない未分化状態である必要があるため、未分化維持機構の解明は医学的な重要性がある。本研究では、ポリコーム遺伝子の二つ、L3MBTL1とFMBT2は未分化状態が不安定になる際に発現して、未分化に戻す役割を果たしていることが示された。これは分化が正しい方向にのみ進むことを補助しているとも言えるもので、再生医療だけでなく、分化研究においても意義深い。
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