Development of pluripotent gene expression indicator using CRISPR/Cas9 genome editing and the study regarding tumorigenicity of human pluripotent stem cell-derived neural stem cells.
| Project/Area Number |
15K06779
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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 |
Neurochemistry/Neuropharmacology
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| Research Institution | Keio University |
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Principal Investigator |
Imai Takao 慶應義塾大学, 医学部(信濃町), 特任助教 (10383712)
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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 |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 神経幹細胞 / 多能性幹細胞 / ゲノム編集 / RNA結合蛋白質 / Oct4 / iPS細胞 |
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| Outline of Final Research Achievements |
This study intended to elucidate the molecular mechanism about the possibility that the neural stem cells produced from pluripotent stem cells such as iPS cells by differentiation induction may become to generate cancer cells. We designed to generate the recombinant human ES-derived neural stem cells that have been genetically modified by genome editing technology using CRISPR / Cas9 in order to evaluate the presence or absence of the microexpression of pluripotent genes that should not normally be expressed in neural stem cells. We also conducted research on the molecular mechanism that makes it difficult for the natural neural stem cells to become cancerous. We found that the interaction between a RNA binding protein and its target RNA contributed to such neural stem cells’ character.
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| Academic Significance and Societal Importance of the Research Achievements |
iPS細胞、ES細胞といったヒト多能性幹細胞から分化誘導した神経幹細胞が内在的要因、外来環境の状態要因によって癌化し得ることについて、本研究過程において有用な知見が得られた。また、内在的なRNA結合蛋白質とRNAの相互作用が、増殖性を保持しつつ癌化しないための一つの分子機構を担っていることが明らかとなった。これらの成果が、ヒト多能性幹細胞から分化誘導された神経幹細胞について癌発生を未然に防ぐ対策の一部として使用されることが将来的に期待され、製剤としての神経幹細胞の品質向上が期待でき、社会に貢献できるものと考えられる。また、増殖性幹細胞と癌細胞の性質の類似点、差異点についての新規知見が得られた。
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Report
(3 results)
Research Products
(3 results)
