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Elucidation of undifferentiated maintaining mechanism of stem cell towards the control of stem cell aging

Research Project

Project/Area Number 18K19646
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 57:Oral science and related fields
Research InstitutionOkayama University

Principal Investigator

Kuboki Takuo  岡山大学, 医歯薬学総合研究科, 教授 (00225195)

Co-Investigator(Kenkyū-buntansha) 大野 充昭  岡山大学, 医歯薬学総合研究科, 准教授 (60613156)
宝田 剛志  岡山大学, 医歯薬学総合研究科, 研究教授 (30377428)
渡辺 亮  京都大学, 医学研究科, 研究員 (60506765)
大野 彩 (木村彩)  岡山大学, 大学病院, 助教 (20584626)
秋山 謙太郎  岡山大学, 大学病院, 講師 (70423291)
升井 伸治  山梨大学, 大学院総合研究部, 特任准教授 (20342850)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywords幹細胞 / 老化 / iPS干渉 / 転写因子 / iPS干渉法 / 間葉系幹細胞 / ステムセルエイジング
Outline of Final Research Achievements

Stem cells are required for lifelong homeostasis and regeneration of organs and tissues in mammals. However, aging of stem cells reduces cellular function and results in dysfunctional organs and tissues. Therefore, maintenance of the stemness of stem cells is of crucial importance, although its mechanisms are still unclear. The aim of this study was to identify the master regulator for the maintenance of stemness of bone marrow mesenchymal stem cells (BMSCs). First, we compared the RNA expression patterns between BMSCs derived from young and old mice, as well as between human BMSCs and human dermal fibroblasts using RNA-seq, and found that 30 transcription factors were highly expressed in BMSCs derived from young mice and in human BMSCs. Next, we found that several transcription factors could inhibit the induction to pluripotent stem (iPS) cells using iPS interfering method. The detailed function of these transcription factors in BMSCs are now being investigated.

Academic Significance and Societal Importance of the Research Achievements

本申請研究の成果は,幹細胞の老化を防ぐことによって,各種加齢性疾患の予防や治療に寄与するという全く新しい概念の提供に繋がると考える.また,本研究成果のさらなる発展により,MSCsの未分化性を維持する技術の開発やMSCsの誘導技術の応用に繋がると考える.これにより,全世界が目指しているiPS細胞からがん化しにくいMSCsを大量に作製するという夢の技術に結びつく可能性を秘めている.

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (7 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] DNA Methylation-Based Regulation of Human Bone Marrow-Derived Mesenchymal Stem/Progenitor Cell Chondrogenic Differentiation.2019

    • Author(s)
      Nomura Y, Hara E.S, Yoshioka Y, Nguyen H.T, Nosho S, Komori T, Ishibashi K, Oohashi T, Ono M, Kuboki T.
    • Journal Title

      Cells Tissues Organs

      Volume: 207 Issue: 3-4 Pages: 115-126

    • DOI

      10.1159/000502885

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A multi-centered epidemiological study evaluating the validity of the treatment difficulty indices developed by the Japan Prosthodontic Society.2018

    • Author(s)
      Kuboki T, Ichikawa T, Baba K, Fujisawa M, Sato H, Aita H, Koyama S, Hideshima M, Sato Y, Wake H, Kimura-Ono A, Nagao K, Kodaira-Ueda Y, Tamaki K, Sadamori S, Tsuga K, Nishi Y, Sawase T, Koshino H, Masumi SI, Sakurai K, Ishibashi K, Ohyama T, Akagawa Y, Hirai T, Sasaki K, Koyano K, Yatani H, Matsumura H
    • Journal Title

      Journal of Prosthodontic Reserach

      Volume: 62(2) Pages: 162-170

    • NAID

      130006733088

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium.2018

    • Author(s)
      Komori T, Ono M, Hara ES, Ueda J, Nguyen HTT, Nguyen HT, Yonezawa T, Maeba T, Ono A, Takarada T, Momota R, Maekawa K, Kuboki T, Oohashi T
    • Journal Title

      Scientific Reports

      Volume: 8(1) Pages: 2612-2612

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] scRNA-Seq解析を応用したマウス歯胚発生メカニズムの解明の試み2020

    • Author(s)
      枝松 緑,小川美帆,井出亮太郎,窪木拓男,大橋俊孝,辻 孝,大野充昭
    • Organizer
      岡山大学次世代研究拠点シンポジウム 2020
    • Related Report
      2019 Annual Research Report
  • [Presentation] Type XVIII collagen modulates the keratinization of oral mucosa2020

    • Author(s)
      Ha Thi Thu Nguyen, Mitsuaki Ono, Emilio Satoshi Hara, Taishi Komori, Midori Edamatsu, Tomoko Yonezawa, Aya Kimura-Ono, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi
    • Organizer
      International Association for Dental Research (IADR) 98th General Session and Exhibition and 49th Annual Meeting of the American Association for Dental Research (AADR)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Biological Regenerative Medicine in Dental Practice -to Attain Reliable and Sophisticated Dental Therapy-.2018

    • Author(s)
      Kuboki T
    • Organizer
      Special Invited Lecture in ACTA 2018.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Collaboration between Soft Tissue Management and Oral Implant Therapy to Attain Optium Esthetic Result.2018

    • Author(s)
      Kuboki T
    • Organizer
      Special Lecture in Haiphong 2018.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-07-25   Modified: 2021-02-19  

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