| Project/Area Number |
18K09468
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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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| Review Section |
Basic Section 56060:Ophthalmology-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Masuda Tomohiro 国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (30796496)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 立体網膜 / iPS細胞 / 分化誘導 / 網膜 / DKK1 / MSX2 / 網膜オルガノイド / ATAC-seq / iPS / 分化 / セルサイクル / クロマチン構造 / 細胞周期 / Fucci / バラツキ |
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| Outline of Final Research Achievements |
The three-dimensional retina (3D retina) that is produced from iPS cells and has a three-dimensional structure similar to that of the in vivo retina. 3D retina is expected to be used for transplantation, pathological analysis of retinal degenerative diseases, drug discovery, and the like. However, it is difficult to induce with good reproducibility, and the variation in the results hinders disease modeling and drug discovery development.
The aim of this study is to elucidate the molecular mechanism that play important role in the retinal differentiation from iPS cells. As a result, it was shown that the expression of the DKK1 gene, which plays an important role in the early stage of retinal differentiation induction, was significantly increased in the high-quality three-dimensional retina by the third day of differentiation. Furthermore, we obtained the result that the gene called MSX2 regulates the expression of the DKK1 gene.
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| Academic Significance and Societal Importance of the Research Achievements |
網膜分化誘導開始から３日後程度の非常に初期の段階において将来的な立体網膜の品質の善し悪しを見分ける分子マーカー（DKK1とMSX2）を明らかにした。
今回の成果は、分化不良個体の分化初期段階での除去や、これらの遺伝子の発現をコントロールすることによる安定的な高品質立体網膜の作製につながると考えている。その結果、立体網膜作製にかかるコストの削減や、網膜変性疾患の病態解析、創薬などをより効率的に進めることが期待できる。
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