Regulatory mechanism of neural stem cells revealed by optical manipulation of gene expressions
| Project/Area Number |
18H02449
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 44020:Developmental biology-related
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| Research Institution | Kyoto University |
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Principal Investigator |
Imayoshi Itaru 京都大学, 生命科学研究科, 教授 (60543296)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Keywords | 神経幹細胞 / ニューロン新生 / 光遺伝学 / 転写因子 / 海馬 / 嗅覚 / 神経発生 / 神経再生 / ライブイメージング / 休眠 / 細胞分化 / 神経新生 / 遺伝子発現 |
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| Outline of Final Research Achievements |
We have succeeded in optimizing PA-Tet gene expression system. The gene expression control activity of PA-Tet can be regulated by Dox and blue light. By using PA-Tet system, we manipulated gene expression in neural stem cells and analyzed the molecular mechanism underlying processes in activation from quiescent state and neuronal differentiation. In addition, we showed neural stem cells in the adult mouse brain can also be controlled by light with the developed PA-Tet gene expression system. From these achievements, we showed that the dynamic gene expression changes in Ascl1 and Hes1 are critically important for regulations of neural stem cells.
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| Academic Significance and Societal Importance of the Research Achievements |
我々が独自に開発した遺伝子発現の光操作システムを用いることで、神経幹細胞において、遺伝子発現を光操作することが可能になった。それにより、Ascl1やHes1などの転写因子や、Notchシグナルエフェクターのダイナミックな発現変化が、神経幹細胞の分化制御に与える影響を明らかにすることができた。加えて、光操作の手法を適応することで、マウス脳内に存在する神経幹細胞の光コントロールが可能なことを実証した。これらの成果は、脳神経系の再生医療技術の発展に貢献するものであると考えられる。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Cholecystokinin-expressing Interneurons of the Medial Prefrontal Cortex Mediate Working Memory Retrieval.2020
Author(s)
Nguyen, R., Venkatesan, S., Binko, M., Yoon Bang, J., Cajanding, J.D., Briggs, C., Sargin, D., Imayoshi, I., Lambe, E.K. and Chul Kim, J.
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Journal Title
J Neurosci.
Volume: 40
Issue: 11
Pages: 2314-2331
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Enhanced lysosomal degradation maintains the quiescent state of neural stem cells2019
Author(s)
T. Kobayashi, W. Piao, T. Takamura, H. Kori, H. Miyachi, S. Kitano, Y. Iwamoto, M. Yamada, I. Imayoshi, S. Shioda, A. Ballabio, R. Kageyama
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Journal Title
Nature Communications
Volume: 10
Issue: 1
Pages: 5446-5446
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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