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Regulatory mechanism of neural stem cells revealed by optical manipulation of gene expressions

Research Project

Project/Area Number 18H02449
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionKyoto University

Principal Investigator

Imayoshi Itaru  京都大学, 生命科学研究科, 教授 (60543296)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
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)
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
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.

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (18 results)

All 2020 2019 2018 Other

All Int'l Joint Research (2 results) Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 8 results)

  • [Int'l Joint Research] Psychology Department/University of Toronto(カナダ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Department of Developmental Biology/Hagedorn Research Institute(デンマーク)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Optimization of light-inducible Gal4/UAS gene expression system in mammalian cells.2020

    • Author(s)
      Yamada, M., Nagasaki, C.S., Suzuki, Y., Hirano, Y. and *Imayoshi, I.
    • Journal Title

      iScience

      Volume: 23 Pages: 101506-101506

    • NAID

      120006884197

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Light-induced silencing of neural activity in Rosa26 knock-in and BAC transgenic mice conditionally expressing the microbial halorhodopsin eNpHR3.2020

    • Author(s)
      Imayoshi I, Tabuchi S, Matsumoto M, Kitano S, Miyachi H, Kageyama R, Yamanaka A
    • Journal Title

      Sci Rep

      Volume: 10(1) Issue: 1 Pages: 3191-3191

    • DOI

      10.1038/s41598-020-59984-3

    • NAID

      120006878490

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Jag1 Modulates an Oscillatory Dll1-Notch-Hes1 Signaling Module to Coordinate Growth and Fate of Pancreatic Progenitors2020

    • Author(s)
      Seymour Philip Allan、Collin Caitlin Alexis、Egeskov-Madsen Anuska la Rosa、Jorgensen Mette Christine、Shimojo Hiromi、Imayoshi Itaru、de Lichtenberg Kristian Honnens、Kopan Raphael、Kageyama Ryoichiro、Serup Palle
    • Journal Title

      Developmental Cell

      Volume: 52 Issue: 6 Pages: 731-747

    • DOI

      10.1016/j.devcel.2020.01.015

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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.
    • Journal Title

      J Neurosci.

      Volume: 40 Issue: 11 Pages: 2314-2331

    • DOI

      10.1523/jneurosci.1919-19.2020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Light-mediated Control of Gene Expression in Mammalian Cells.2020

    • Author(s)
      Yamada M, Nagasaki C. S, Ozawa T, Imayoshi I.
    • Journal Title

      Neuroscience Research

      Volume: 152 Pages: 66-77

    • DOI

      10.1016/j.neures.2019.12.018

    • NAID

      120006888020

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High Hes1 expression and resultant Ascl1 suppression regulate quiescent vs. active neural stem cells in the adult mouse brain2019

    • Author(s)
      Sueda Risa、Imayoshi Itaru、Harima Yukiko、Kageyama Ryoichiro
    • Journal Title

      Genes & Development

      Volume: 33 Issue: 9-10 Pages: 511-523

    • DOI

      10.1101/gad.323196.118

    • NAID

      120006591371

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [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
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 5446-5446

    • DOI

      10.1038/s41467-019-13203-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Light Control of the Tet Gene Expression System in Mammalian Cells2018

    • Author(s)
      Yamada Mayumi、Suzuki Yusuke、Nagasaki Shinji C.、Okuno Hiroyuki、Imayoshi Itaru
    • Journal Title

      Cell Reports

      Volume: 25 Issue: 2 Pages: 487-500

    • DOI

      10.1016/j.celrep.2018.09.026

    • NAID

      120006531246

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 発生発達期暴露による嗅球神経新生影響~毒性評価としての嗅球利用を探る~2020

    • Author(s)
      今吉 格
    • Organizer
      第47回日本毒性学会学術年会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Toward understanding and manipulation of neural bases underlying animal behaviors and psychiatric diseases2020

    • Author(s)
      今吉 格
    • Organizer
      第43回日本分子生物学会年会シンポジウム
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Regulatory mechanism of neural stem cells revealed by optical manipulation of gene expressions2020

    • Author(s)
      今吉 格
    • Organizer
      第11回新潟大学脳研究所共同研究拠点国際シンポジウム
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 神経幹細胞の制御機構 と生後脳ニューロン新生2019

    • Author(s)
      今吉 格
    • Organizer
      第21回 京都大学・生命科学研究科シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 遺伝子発現の光操作技術 と神経幹細胞研究への応用2019

    • Author(s)
      今吉 格
    • Organizer
      Chemistry For Neuroscience 2019
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Regulatory mechanism of neural stem cells revealed by optical manipulation of gene expressions2019

    • Author(s)
      今吉 格
    • Organizer
      ExCELLS若手リトリート
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Regulatory mechanism of neural stem cells revealed by optical manipulation of gene expressions2018

    • Author(s)
      今吉 格
    • Organizer
      第17回幹細胞シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regulatory mechanism of neural stem cells revealed by optical manipulation of gene expressions2018

    • Author(s)
      今吉 格
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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