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Induction of Mesenchymal Stem Cells from Somatic Cells by Direct Reprograming/Transdifferentiaition

Research Project

Project/Area Number 26861217
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionKindai University

Principal Investigator

TERAMURA Takeshi  近畿大学, 医学部附属病院, 講師 (40460901)

Research Collaborator ASAHARA Hiroshi  東京医科歯科大学, 医学部, 教授
Lotz Martin  スクリプス研究所, 分子実験医学部門, 教授
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords再生医療 / 間葉系幹細胞 / リプログラミング / ダイレクトリプログラミング / 上皮間葉転換 / 転写因子 / Twist1 / TGFβシグナル / iPS細胞
Outline of Final Research Achievements

Mesenchymal stem cells (MSCs) are multipotent stem cells that are present in multiple tissues. Recent studies demonstrated that MSCs can support wound healing and tissue regeneration. On the other hand, adult MSCs exhibit cellular senescence during ex vivo expansion, which is accompanied by a reduction in self-renewal and multidifferentiation potential. To resolve this, identification of master molecules and central cascades involving MSC self-renewal is essential. Here, we focused on Twist1, which is a master regulator of epithelial-mesenchymal transition (EMT), and examined it’s roles in MSCs. Suppression of Twist1 leaded to reduction of Sox2, Bmi1, and Gata6 expressions. Contrary, over-expression of Twist1 induced expression of these genes. Mass spectrometric analysis showed that Tiwist1 involves epigenetic modification. Finally, we demonstrated that direct induction of MSCs from human monocytes was possible by introduce Twist1 with reprogramming factors.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (5 results)

All 2017 2016 2015

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 (1 results) (of which Invited: 1 results)

  • [Journal Article] TWIST1 induces MMP3 expression through up-regulating DNA hydroxymethylation and promotes catabolic responses in human chondrocytes.2017

    • Author(s)
      Hasei J, Teramura T, Takehara T, Onodera Y, Horii T, Olmer M, Hatada I, Fukuda K, Ozaki T, Lotz M, Asahara H*.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 42990-42990

    • DOI

      10.1038/srep42990

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Inflammation-induced miRNA-155 inhibits self-renewal of neural stem cells via suppression of CCAAT/enhancer binding protein β (C/EBPβ) expression2017

    • Author(s)
      Obora K, Onodera Y, Takehara T, Frampton J, Hasei J, Ozaki T, Teramura T, Fukuda K
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 43604-43604

    • DOI

      10.1038/srep43604

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cdh2 stabilizes FGFR1 and contributes to primed-state pluripotency in mouse epiblast stem cells2015

    • Author(s)
      Toshiyuki Takehara
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 14722-14722

    • DOI

      10.1038/srep14722

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Gene-modified embryonic stem cell test to characterize chemical risks.2015

    • Author(s)
      Kitada K, Kizu A, Teramura T, Takehara T, Hayashi M, Tachibana D, Wanibuchi H, Fukushima S, Koyama M, Yoshida K, Morita T.
    • Journal Title

      Environ Sci Pollut Res Int.

      Volume: 22 Issue: 22 Pages: 18252-18259

    • DOI

      10.1007/s11356-015-5051-0

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 多能性幹細胞からの間葉系幹細胞の分化誘導と軟骨再生2016

    • Author(s)
      寺村岳士、浅原弘嗣、福田寛二
    • Organizer
      日本整形外科学会基礎学術集会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2016-10-13
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2020-01-20  

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