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Identification of the novel mechanism of satellite cell number reduction in sarcopenia

Research Project

Project/Area Number 16K16597
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Applied health science
Research InstitutionNational Center of Neurology and Psychiatry (2017)
Tokyo Medical and Dental University (2016)

Principal Investigator

Hayashi Shinichiro  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 疾病研究第一部, 室長 (10732381)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords骨格筋 / 筋衛星細胞 / サルコペニア / 細胞老化 / Klf5 / 細胞周期 / 筋分化
Outline of Final Research Achievements

Satellite cells, a stem cell population in skeletal muscle, are essential for muscle regeneration. It has been reported that the number of satellite cells and its regenerative capacity declines during aging. We have recently reported that Klf5 is induced during myoblast differentiation and promotes muscle specific gene expression during myogenesis. Here, we observed Klf5 is also weakly expressed in proliferating myoblasts. Klf5 overexpression in C2C12 myoblasts promoted cell cycle arrest and cellular senescence as demonstrated SA-βGal staining. RNA-seq and gene ontology analysis revealed that muscle related- and cell cycle related genes were downregulated by Klf5 overexpression. In addition, Klf5 overexpression induced upregulation of p21. Therefore, these results suggest regulation of KLF5 expression in muscle may be disrupted during aging, and which leads to cellular senescence or promotes a myogenic to fibrogenic fate conversion in satellite cell.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (20 results)

All 2018 2017 2016

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Two novel VCP missense variants identified in Japanese patients with multisystem proteinopathy2018

    • Author(s)
      Inoue Michio, Iida Aritoshi, Hayashi Shinichiro, Mori-Yoshimura Madoka, Nagaoka Atsushi, Yoshimura Shunsuke, Shiraishi Hirokazu, Tsujino Akira, Takahashi Yuji, Nonaka Ikuya, Hayashi K Yukiko, Noguchi Satoru, Nishino Ichizo
    • Journal Title

      Human Genome Variation

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bmal1 regulates inflammatory responses in macrophages by modulating enhancer RNA transcription.2017

    • Author(s)
      Oishi Y, Hayashi S, Isagawa T, Oshima M, Iwama A, Shimba S, Okamura H and Manabe I.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 7086-7086

    • DOI

      10.1038/s41598-017-07100-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] LSD1 Controls Timely MyoD Expression via MyoD Core Enhancer Transcription.2017

    • Author(s)
      Scionti I, Hayashi S, Mouradian S, Girard E, Esteves de Lima J, Morel V, Simonet T, Wurmser M, Maire P, Ancelin K, Metzger E, Schule R, Goillot E, Relaix F, Schaeffer L.
    • Journal Title

      Cell Reports

      Volume: 18 Issue: 8 Pages: 1996-2006

    • DOI

      10.1016/j.celrep.2017.01.078

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice.2016

    • Author(s)
      Hayashi S, Manabe I, Suzuki Y, Relaix F, Oishi Y
    • Journal Title

      eLife

      Volume: -

    • DOI

      10.7554/elife.17462

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 骨格筋幹細胞の新規分化制御機構と筋疾患治療への応用2018

    • Author(s)
      林 晋一郎
    • Organizer
      第54回 お茶の水疾患研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 筋衛星細胞の分化および筋再生におけるKlf5の役割2017

    • Author(s)
      林 晋一郎, 大塚 千聖, 林, 鈴木 裕美, 大石 由美子
    • Organizer
      第5回 骨格筋生物学研究会
    • Place of Presentation
      東京大学, 東京
    • Year and Date
      2017-03-03
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨格筋発生過程におけるKlf5の機能解析2017

    • Author(s)
      大塚 千聖, 林 晋一郎, 鈴木 裕美, 大石 由美子
    • Organizer
      第5回 骨格筋生物学研究会
    • Place of Presentation
      東京大学, 東京
    • Year and Date
      2017-03-03
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨格筋の再生・発生における新規分化制御機構2017

    • Author(s)
      林 晋一郎
    • Organizer
      第3回 日本筋学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Klf5は筋芽細胞の増殖を負に制御し、細胞老化を誘導する2017

    • Author(s)
      林 晋一郎
    • Organizer
      第5回 若手による骨格筋細胞研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 筋衛星細胞の未分化性維持機構の解明と細胞移植治療への応用2017

    • Author(s)
      林 晋一郎
    • Organizer
      「筋ジストロフィー関連疾患の分子病態解明 とそれに基づく診断法・治療法開発」(29-4) 西野班 班会議
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 骨格筋細胞の新規老化メカニズム解析2017

    • Author(s)
      林 晋一郎、真鍋 一郎、西野 一三、大石 由美子
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Klf5 is involved in the pathogenesis of muscle atrophy2017

    • Author(s)
      Liu Lin, Shinichiro Hayashi, Yumiko Oishi
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] 骨格筋発生におけるKlf5の機能解析2016

    • Author(s)
      林 晋一郎、 大塚千聖、 鈴木 裕美、 真鍋一郎、 大石 由美子
    • Organizer
      第39回 分子生物学会年会
    • Place of Presentation
      パシフィコ横浜, 横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨格筋の分化、再生、発生におけるKlf5の役割2016

    • Author(s)
      林 晋一郎
    • Organizer
      第四回 若手による骨格筋細胞研究会
    • Place of Presentation
      ウインクあいち, 名古屋
    • Year and Date
      2016-11-14
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨格筋発生におけるKlf5の機能解析2016

    • Author(s)
      林 晋一郎、 大塚千聖、 鈴木 裕美、 真鍋一郎、 大石 由美子
    • Organizer
      Molecular Cardiovascular Conference II (2016)
    • Place of Presentation
      東京ドームホテル, 東京
    • Year and Date
      2016-09-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Klf5 regulates skeletal muscle differentiation by directly targeting muscle-specific genes2016

    • Author(s)
      Shinichiro Hayashi, Ichiro Manabe, Yumi Suzuki and Yumiko Oishi
    • Organizer
      FASEB Science Research Conferences, KLF and Sp Transcription Factors in Disease and Regenerative Medicine
    • Place of Presentation
      Snowmass, Co, USA
    • Year and Date
      2016-08-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 筋衛星細胞における新規筋分化制御機構の解明2016

    • Author(s)
      林 晋一郎、 大塚千聖、 鈴木 裕美、 真鍋一郎、 大石 由美子
    • Organizer
      第二回日本筋学会学術集会
    • Place of Presentation
      国立精神・神経医療研究センター, 東京
    • Year and Date
      2016-08-05
    • Related Report
      2016 Research-status Report
  • [Presentation] 骨格筋発生におけるKlf5の機能解析2016

    • Author(s)
      大塚 千聖, 林 晋一郎, 鈴木 裕美, 大石 由美子
    • Organizer
      第二回日本筋学会学術集会
    • Place of Presentation
      国立精神・神経医療研究センター, 東京
    • Year and Date
      2016-08-05
    • Related Report
      2016 Research-status Report
  • [Book] 超高齢社会に挑む骨格筋のメディカルサイエンス2018

    • Author(s)
      武田伸一、林晋一郎、青木吉嗣、秋本崇之、吾郷由希夫、東浩太郎、池田和博、井上聡、今井祐記、上住聡芳、上住円、内田信一、江口貴大、大川恭行、大澤裕、小川純人、小川渉、小野悠介、鍵田明宏、梶村真吾、金川基、上村大輔 他
    • Total Pages
      230
    • Publisher
      羊土社
    • ISBN
      9784758103701
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 筋サテライト細胞の培養方法2017

    • Inventor(s)
      大石 由美子、林 晋一郎
    • Industrial Property Rights Holder
      大石 由美子、林 晋一郎
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-121787
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-12-27  

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