| Project/Area Number |
17K10108
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
北畠 康司 大阪大学, 医学部附属病院, 准教授 (80506494)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | iPS細胞 / ゲノム編集 / ダウン症候群 / ゲノム編集技術 / 染色体異常 / 幹細胞 / 造血 |
|---|
| Outline of Final Research Achievements |
In Down's syndrome, various complications occur due to the effect of the number of genes on chromosome 21. Therefore, in this study, we aimed to establish a cell model system that enables identification of pathologically responsible genes in Down's syndrome by combining human iPS cells, genome editing technology, and human XIST genes.
XIST was inserted into chromosome 21 under the control of the TET induction system, and it was confirmed that gene expression was suppressed by XIST in a Doxycycline-dependent manner. By inducing the differentiation of these XIST-iPS cells into astrocytes, we found that the proliferation rate of astrocytes was abnormally updated in Down's syndrome, and succeeded in identifying DYRK1A and PIGP as the genes.
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| Academic Significance and Societal Importance of the Research Achievements |
ダウン症候群は精神発達遅滞をもたらす遺伝性疾患では最多である。その平均寿命は60歳を越えており病態解明が求められている。本研究により病態責任遺伝子の同定が可能となった。また実際にダウン症剖検脳で見られるアストロサイトの増殖の鍵を握る遺伝子を見つけることができた。
今後このメカニズムを深く追求することで、治療法の開発に一歩近づくことができるだろう。
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