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Crosstalk between immune system and nervous system in the pathogenesis of spinal cord injury

Research Project

Project/Area Number 26713047
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypePartial Multi-year Fund
Research Field Orthopaedic surgery
Research InstitutionKeio University

Principal Investigator

KOHYAMA JUN  慶應義塾大学, 医学部(信濃町), 准教授 (30437511)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥23,530,000 (Direct Cost: ¥18,100,000、Indirect Cost: ¥5,430,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords脊髄損傷 / Notchシグナル / エピジェネティクス / 神経科学 / オリゴデンドロサイト前駆細胞
Outline of Final Research Achievements

To unravel mechanistic insight in progression of spinal cord injury, I focused on the interaction between the immune system and the nervous system. I initially discovered activation of Sox2 exprssion in the injured site and,importantly, the Sox2-positive cells were surrounded by microglial cells. To further clarify the mechanism of Sox2 upregulation, we characterized the cells and found that these cells were oligodendrocyte precursor cells (OPCs). At the site of spinal cord injury, immune cell accumulation was observed after injury, and these immune cells expressed ligand for Notch signaling. Then, proliferation of OPCs was activated by Notch signaling. Furthermore, conditional knockout of RBP-J, an effector of Notch signaling, in OPCs resulted in defect in activation of OPCs, indicating that interaction between immune system and nervous system, which was mediated by Notch signaling is important for pathogenesis of spinal cord injury.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (6 results)

All 2018 2017 2016 2015 2014

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (1 results)

  • [Journal Article] Chromatin remodeler CHD7 regulates the stem cell identity of human neural progenitors2018

    • Author(s)
      Chai MuhChyi、Sanosaka Tsukasa、Okuno Hironobu、Zhou Zhi、Koya Ikuko、Banno Satoe、Andoh-Noda Tomoko、Tabata Yoshikuni、Shimamura Rieko、Hayashi Tetsutaro、Ebisawa Masashi、Sasagawa Yohei、Nikaido Itoshi、Okano Hideyuki、Kohyama Jun
    • Journal Title

      Genes & Development

      Volume: 32 Issue: 2 Pages: 165-180

    • DOI

      10.1101/gad.301887.117

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low immunogenicity of mouse induced pluripotent stem cell-derived neural stem/progenitor cells2017

    • Author(s)
      Itakura Go、Ozaki Masahiro、Nagoshi Narihito、Kawabata Soya、Nishiyama Yuichiro、Sugai Keiko、Iida Tsuyoshi、Kashiwagi Rei、Ookubo Toshiki、Yastake Kaori、Matsubayashi Kohei、Kohyama Jun、Iwanami Akio、Matsumoto Morio、Nakamura Masaya、Okano Hideyuki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41598-017-13522-w

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Whole-Genome DNA Methylation Analyses Revealed Epigenetic Instability in Tumorigenic Human iPS Cell-Derived Neural Stem/Progenitor Cells.2017

    • Author(s)
      Iida T, Iwanami A, Sanosaka T, Kohyama J, Miyoshi H, Nagoshi N, Kashiwagi R, Toyama Y, Matsumoto M, Nakamura M, Okano H.
    • Journal Title

      Stem Cells

      Volume: 35 Issue: 5 Pages: 1316-1327

    • DOI

      10.1002/stem.2581

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Grafted human iPS cell-derived oligodendrocyte precursor cells contribute to robust remyelination of demyelinated axons after spinal cord injury2016

    • Author(s)
      Kawabata S, Takano M, Numasawa-Kuroiwa Y, Itakura G, Kobayashi Y, Nishiyama Y, Sugai K, Nishimura S, Iwai H, Isoda M, Shibata S, Kohyama J, Iwanami A, Toyama Y, Matsumoto M, Nakamura M, Okano H,
    • Journal Title

      Stem Cell Reports

      Volume: 6(1) Issue: 1 Pages: 1-8

    • DOI

      10.1016/j.stemcr.2015.11.013

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] TLR9 signaling in microglia attenuates seizure-induced aberrant neurogenesis in the adult hippocampus2015

    • Author(s)
      Matsuda T., Murao N., Katano Y., Juliandi B., Kohyama J., Akira S., Kawai T. & Nakashima K
    • Journal Title

      Nat Commun

      Volume: 6 Issue: 1 Pages: 6514-6514

    • DOI

      10.1038/ncomms7514

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] マウス脊髄損傷モデルにおけるエピジェネティック修飾関連因子の解析2014

    • Author(s)
      43.堀桂子, 神山淳, 坂野聡重, 岩波明生, 岡野栄之, 戸山芳昭, 中村雅也
    • Organizer
      第29回日本整形外科学会基礎学術集会
    • Place of Presentation
      城山観光ホテル(鹿児島県鹿児島市)
    • Year and Date
      2014-10-09 – 2014-10-10
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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