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Novel stemness markers in murine adipose-derived stem cells

Research Project

Project/Area Number 17H05030
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Food science
Research InstitutionUniversity of Shizuoka

Principal Investigator

Yamaguchi Masahiko  静岡県立大学, 薬学部, 助教 (00632639)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥20,930,000 (Direct Cost: ¥16,100,000、Indirect Cost: ¥4,830,000)
Fiscal Year 2019: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2017: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Keywords組織幹細胞 / 生活習慣病 / 肥満 / 核内受容体 / 栄養 / 脂肪組織 / 栄養学 / 幹細胞
Outline of Final Research Achievements

Obesity is associated with proliferation and differentiation of adipose-derived stem cells (ADSCs) into mature adipocytes. Nutritional stimuli induce ADSCs proliferation and differentiation, and this process is well established because master regulators of adipogenic differentiation, C/EBPalpha and PPARgamma were identified. However, under normal condition, molecular mechanisms to maintain stemness of ADSCs are largely unknown.
To identify genes essential for the maintenance, microarray analysis was performed on murine ADSCs and 4-day cultured ADSCs (preadipocytes). Among the 223 up-regulated transcriptional factor genes in ADSCs, we focused on nuclear receptor 4a (Nr4a) family, which play diverse roles including metabolic processes. Nr4a-overexpressed preadipocytes showed reduced accumulation of lipid droplet and decreased expressions of C/EBPalpha and PPARgamma. ChIP analysis confirmed that Nr4a directly bound to C/EBPalpha and PPARgamma promotor.

Academic Significance and Societal Importance of the Research Achievements

脂肪幹細胞においてNr4a family が未分化性維持に寄与していることが示唆された。この結果は脂肪分化のON/OFFを決定づける分子機構の解明に繋がるため、脂肪幹細胞をターゲットとして肥満を予防する分子標的薬の探索へと発展させることが期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (31 results)

All 2019 2018 2017 2016 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results) Presentation (24 results) (of which Int'l Joint Research: 8 results) Remarks (3 results)

  • [Journal Article] Elevation of sensitivity to anticancer agents of human lung adenocarcinoma A549 cells by knockdown of claudin-2 expression in monolayer and spheroid culture models.2018

    • Author(s)
      Maruhashi R, Akizuki R, Sato T, Matsunaga T, Endo S, Yamaguchi M, Yamazaki Y, Sakai H, Ikari A
    • Journal Title

      Biochim Biophys Acta Mol Cell Res.

      Volume: 1865 Pages: 470-479

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elevation of sensitivity to anticancer agents of human lung adenocarcinoma A549 cells by knockdown of claudin-2 expression in monolayer and spheroid culture models2018

    • Author(s)
      Maruhashi Ryohei、Akizuki Risa、Sato Tomonari、Matsunaga Toshiyuki、Endo Satoshi、Yamaguchi Masahiko、Yamazaki Yasuhiro、Sakai Hideki、Ikari Akira
    • Journal Title

      Biochimica et Biophysica Acta

      Volume: 1865 Issue: 3 Pages: 470-479

    • DOI

      10.1016/j.bbamcr.2017.12.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The RING finger- and PDZ domain-containing protein PDZRN3 controls localization of the Mg2+ regulator claudin-16 in renal tube epithelial cells.2017

    • Author(s)
      Marunaka Kana、Furukawa Chisa、Fujii Naoko、Kimura Toru、Furuta Takumi、Matsunaga Toshiyuki、Endo Satoshi、Hasegawa Hajime、Anzai Naohiko、Yamazaki Yasuhiro、Yamaguchi Masahiko、Ikari Akira
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 31 Pages: 13034-13044

    • DOI

      10.1074/jbc.m117.779405

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Up-regulation of transient receptor potential melastatin 6 channel expression by tumor necrosis factor-α in the presence of epidermal growth factor receptor tyrosine kinase inhibitor2016

    • Author(s)
      Furukawa C, Fujii N, Manabe A, Matsunaga T, Endo S, Hasegawa H, Ito Y, Yamaguchi M, Yamazaki Y, Ikari A
    • Journal Title

      Journal of Cellular Physiology

      Volume: 印刷中 Issue: 10 Pages: 2841-2850

    • DOI

      10.1002/jcp.25709

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 脂肪幹細胞の未分化性維持におけるNuclear receptor 4aの機能解析2019

    • Author(s)
      山口賢彦、寺阪祐紀、西山麗紗、黒川洵子
    • Organizer
      第65回日本薬学会東海支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Roles of nuclear receptor 4a family in maintenance of stemness of murine adipose-derived stem cells2019

    • Author(s)
      Masahiko Yamaguchi, Kenta Ito, Yuki Terasaka, Risa Nishiyama, and Junko Kurokawa
    • Organizer
      第92回日本薬理学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂肪組織由来間葉系幹細胞の分化過程におけるNuclear receptor 4aの役割2019

    • Author(s)
      山口賢彦、寺阪祐紀、西山麗紗、黒川洵子
    • Organizer
      生体機能と創薬シンポジウム2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] Nuclear receptor 4a family を介した 脂肪幹細胞の未分化性維持機構の解析2019

    • Author(s)
      鈴木一生、山口賢彦、寺坂祐紀、西山麗紗、黒川洵子
    • Organizer
      日本病院薬剤師会東海ブロック・ 日本薬学会東海支部合同学術大会2019
    • Related Report
      2019 Annual Research Report
  • [Presentation] A molecular switch regulating adipose-derived stem cell differentiation2019

    • Author(s)
      Issei Suzuki, Masahiko Yamaguchi, Yuki Terasaka, Risa Nishiyama, and Junko Kurokawa
    • Organizer
      第 24 回静岡健康・長寿学術フォーラム
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マウス脂肪幹細胞の未分化性維持における Nr4a family の機能解析2019

    • Author(s)
      寺阪 祐紀、西山 麗紗、鈴木 一生、山口 賢彦、黒川 洵子
    • Organizer
      第21回応用薬理シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脂肪組織由来間葉系幹細胞の未分化性維持における Nuclear receptor 4a2 の機能解析2019

    • Author(s)
      寺阪 祐紀 , 伊藤 謙汰 , 西山 麗紗 , 山口 賢彦 , 黒川 洵子
    • Organizer
      第139回 日本薬学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Nuclear receptor 4a familyを介した脂肪幹細胞の未分化性維持機構の解析2018

    • Author(s)
      伊藤謙汰、石村裕樹、山口賢彦、黒川洵子
    • Organizer
      第64回日本薬学会東海支部総会・大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Novel receptors for maintenance of stemness in murine adipose-derived stem cells.2018

    • Author(s)
      Masahiko Yamaguchi, Mana Takahashi, Kenta Ito, Hiroki Ishimura, Junko Kurokawa
    • Organizer
      WCP2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脂肪幹細胞において高発現するGタンパク質共役型受容体の脂肪分化に対する作用解析2018

    • Author(s)
      高橋茉那、山口賢彦、黒川洵子
    • Organizer
      第4回 次世代を担う若手のためのレギュラトリーサイエンスフォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nuclear receptor 4a family を介した脂肪幹細胞の未分化性維持機構の解析2018

    • Author(s)
      伊藤謙汰、西山麗紗、山口賢彦、黒川洵子
    • Organizer
      第4回 次世代を担う若手のためのレギュラトリーサイエンスフォーラム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Roles of nuclear receptor 4a family in maintenance of adipose-derived stem cells.2018

    • Author(s)
      Kenta Ito, Hiroki Ishimura, Masahiko Yamaguchi Junko Kurokawa
    • Organizer
      The 4th International Conference on Pharma and Food
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Localization of YAP in the differentiation process of murine adipose stem cells2018

    • Author(s)
      Chiho Okada, Masahiko Yamaguchi, Junko Kurokawa
    • Organizer
      The 4th International Conference on Pharma and Food
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of G-protein-coupled receptor 3 in adipogenic differentiation of adipose-derived stem cells.2018

    • Author(s)
      Mana Takahashi, Masahiko Yamaguchi, Junko Kurokawa
    • Organizer
      The 4th International Conference on Pharma and Food
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of nuclear receptor 4a in maintenance of stemness of murine adipose-derived stem cells.2018

    • Author(s)
      Masahiko Yamaguchi, Kenta Ito, Mana Takahashi, Risa Nishiyama, and Junko Kurokawa
    • Organizer
      the 13th Japan-China International Symposium on Health Sciences
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of nuclear receptor 4a family in maintenance of stemness of murine adipose-derived stem cells2018

    • Author(s)
      Masahiko Yamaguchi, Kenta Ito, Yuki Terasaka,
    • Organizer
      The 92nd Annual Meeting of The JPS
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nuclear receptor 4a family を介した脂肪幹細胞の未分化性維持の細胞内制御機構の解析  2018

    • Author(s)
      伊藤謙汰、石村裕樹、山口賢彦、黒川洵子
    • Organizer
      日本薬学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウス脂肪幹細胞の分化機構におけるYes-associated protein の基礎的検討2018

    • Author(s)
      岡田千穂、山口賢彦、黒川洵子
    • Organizer
      日本薬学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Novel stemness markers in murine adipose-derived stem cell2017

    • Author(s)
      11.12.Masahiko Yamaguchi, Hiroki Ishimura, Kenta Ito, Yasuhiro Yamazaki, Junko Sugatani, Junko Kurokawa
    • Organizer
      Ion Channel Modulation Symposium,
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脂肪幹細胞における核内受容体Nr4aの細胞内局在および機能の解析2017

    • Author(s)
      石村裕樹、山口賢彦、山崎泰広、菅谷純子、黒川洵子
    • Organizer
      第63回日本薬学会東海支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪由来間葉系幹細胞の遺伝子発現および増殖・脂肪分化における性差解析2017

    • Author(s)
      水口敦史、山口賢彦、山崎泰広、黒川洵子
    • Organizer
      第63回日本薬学会東海支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪組織由来間葉系幹細胞の増殖・脂肪分化に対するGタンパク質共役型受容体の機能解析2017

    • Author(s)
      高橋茉那、山口賢彦、山崎泰広、菅谷純子、黒川洵子
    • Organizer
      第63回日本薬学会東海支部総会・大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 脂肪組織由来間葉系幹細胞において高発現するPou3f1の機能解析2017

    • Author(s)
      木村亮介、山口賢彦、山崎泰広、黒川洵子
    • Organizer
      生体機能と創薬シンポジウム2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] An origin of sex differences in coronary arteries of embryonic mice.2017

    • Author(s)
      Yamaguchi M, Kodama M, Okuno R, Arima Y, Nishiyama K, Kurihara H, Kurokawa J
    • Organizer
      8th Congress of the International Society for Gender Medicine
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 静岡県立大学薬学部 生体情報分子解析学分野のホームページ

    • URL

      https://w3pharm.u-shizuoka-ken.ac.jp/rinsho/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 静岡県立大学薬学部 生体情報分子解析学分野HP

    • URL

      https://w3pharm.u-shizuoka-ken.ac.jp/rinsho/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 静岡県立大学薬学部生体情報分子解析学分野

    • URL

      http://w3pharm.u-shizuoka-ken.ac.jp/rinsho/index.html

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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