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Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds

Research Project

Project/Area Number 16K15222
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General medical chemistry
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Dai Ping  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (20291924)

Co-Investigator(Kenkyū-buntansha) 武田 行正  京都府立医科大学, 医学(系)研究科(研究院), 助教 (40735552)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsダイレクトリプログラミング / 褐色脂肪細胞 / 細胞移植治療 / 再生医療 / 低分子化合物 / 再生医学 / ダイレクトリプログラミン / 糖尿病 / 糖・脂質代謝
Outline of Final Research Achievements

Brown adipocytes maintain body temperature by burning lipid, which can prevent obese and diabetes by enhancing energy expenditure. Brown adipocytes are differentiated from induced pluripotent stem cells (iPSCs) and directly converted from fibroblasts by virus vector-mediated expression of a specific set of transcription factors. In order to provide a safer approach to generate brown adipocytes, we developed chemical compound-based direct conversion from human dermal fibroblasts into brown adipocytes without any genetic manipulation. The chemical compound-induced brown adipocytes (ciBAs) exhibit expression of human brown adipocyte-specific genes including Ucp1, activation of thermogenic gene expression through adrenergic receptor, and increased oxygen consumption rates. Our findings might provide an easily accessible approach for generating human brown adipocytes from fibroblasts and offer therapeutic potential for the management of obesity, diabetes, and related metabolic disorders.

Report

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

    (10 results)

All 2018 2017 2016

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (4 results) (of which Invited: 2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] 低分子化合物を用いた再生医療用細胞のダイレクトリプログラミング2018

    • Author(s)
      戴平、武田行正
    • Journal Title

      京都府立医科大学雑誌

      Volume: 127 Pages: 1-12

    • NAID

      40021465056

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemical compound-based direct reprogramming for future clinical applications.2018

    • Author(s)
      Takeda Y., Harada Y., Yoshikawa T., Dai P.
    • Journal Title

      Bioscience Reports

      Volume: 38 Issue: 3

    • DOI

      10.1042/bsr20171650

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds.2017

    • Author(s)
      Takeda Y., Harada Y., Yoshikawa T., Dai P.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 4304-4304

    • DOI

      10.1038/s41598-017-04665-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Highly sensitive fluorescence detection of metastatic lymph nodes of gastric cancer with photo-oxidation of protoporphyrin IX2016

    • Author(s)
      Koizumi N, Harada Y, Beika M, Minamikawa T, Yamaoka Y, Dai P, Murayama Y, Yanagisawa A, Otsuji E, Tanaka H, Takamatsu T
    • Journal Title

      European Jounal of Surgical Oncology

      Volume: 42 Issue: 8 Pages: 1236-1246

    • DOI

      10.1016/j.ejso.2016.03.003

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Spatiotemporal Pattern of Glis3 Expression Indicates a Regulatory Function in Bipotent and Endocrine Progenitors during Early Pancreatic Development and in Beta, PP and Ductal Cells.2016

    • Author(s)
      Kang H.S., Takeda Y., Jeon K., and Jetten A.M.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 6 Pages: e0157138-e0157138

    • DOI

      10.1371/journal.pone.0157138

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] シグナル伝達経路制御によるヒト線維芽細胞から褐色脂肪細胞へのダイレクトリプログラミング2018

    • Author(s)
      武田行正、原田義規、戴平
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト皮膚細胞より低分子化合物のみで種々の再生医療用細胞を誘導2017

    • Author(s)
      戴平
    • Organizer
      日本再生医療学会
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] ヒト皮膚細胞より低分子化合物のみで種々の再生医療用細胞を誘導2017

    • Author(s)
      戴平
    • Organizer
      第16回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 低分子化合物を用いたダイレクトリプログラミングによるヒト線維芽細胞から褐色脂肪細胞への直接誘導2017

    • Author(s)
      武田行正、原田義規、戴平
    • Organizer
      第40回日本分子生物学会年会・2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 褐色脂肪細胞を製造する方法、及び組成物2016

    • Inventor(s)
      戴平
    • Industrial Property Rights Holder
      戴平
    • Industrial Property Rights Type
      特許
    • Filing Date
      2016-09-30
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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