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Development of chemical compound-based direct reprogramming method for human retinal pigment epithelial cells

Research Project

Project/Area Number 17K01365
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Kurahashi Toshihiro  京都府立医科大学, 医学(系)研究科(研究院), 講師 (00596570)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords細胞再生医学 / ケミカルダイレクトリプログラミング / 再生医学 / ダイレクトリプログラミング
Outline of Final Research Achievements

Recent studies have demonstrated it is possible to change the cell fate by using only chemical compounds.We aimed to develop a method for directly inducing human retinal pigment epithelium (RPE) cells from human fibroblasts using chemical compounds. We found a combination of chemical compounds that decrease fibroblast-specific gene expression and induce epithelial-like morphology in human fibroblast. In order to evaluate the degree of cell differentiation efficiently, we generated a reporter cell in which the promoter region of RPE-specific gene was incorporated into human fibroblasts. Using the reporter cells, we tried to establish a method for inducing RPE cell differentiation by various compounds, but so far, a method for inducing the expression of RPE-specific genes has not been established.

Academic Significance and Societal Importance of the Research Achievements

研究期間以内にケミカルダイレクトリプログラミングによるRPE細胞の分化誘導法の確立はできなかった。一方で、ヒト線維芽細胞の間葉系細胞マーカー遺伝子の発現を減少させうる低分子化合物の組み合わせに関して興味深い知見を得た。こうした遺伝子発現変化は間葉系細胞から上皮系細胞への運命転換であるMesenchymal-to-epithelial transition (MET)に重要なステップであり、このMETは細胞のリプログラミングにおいて重要であることがこれまでに示されてきている。したがって、本研究によって得られた低分子化合物に関する知見は、引き続き行う細胞リプログラミングの研究に有益であると考える。

Report

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

    (3 results)

All 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results)

  • [Journal Article] Double Knockout of Peroxiredoxin 4 (Prdx4) and Superoxide Dismutase 1 (Sod1) in Mice Results in Severe Liver Failure.2018

    • Author(s)
      Homma T, Kurahashi T, Lee J, Nabeshima A, Yamada S, Fujii J.
    • Journal Title

      Oxid Med Cell Longev

      Volume: 2018 Issue: 1

    • DOI

      10.1155/2018/2812904

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased reproductive performance in xCT-knockout male mice.2017

    • Author(s)
      Hamashima, S., Homma, T., Kobayashi, S., Ishii, N., Kurahashi, T., Watanabe, R., Kimura, N., Sato, H., and Fujii, J.
    • Journal Title

      Free Radic. Res.

      Volume: 51 Issue: 9-10 Pages: 851-860

    • DOI

      10.1080/10715762.2017.1388504

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Protective role of testis-specific peroxiredoxin 4 against cellular oxidative stress2017

    • Author(s)
      Eisuke Tasaki, Shotaro Matsumoto, Hisashi Tada, Toshihiro Kurahashi, Xuhong Zhang, Junichi Fujii, Toshihiko Utsumi, Yoshihito Iuchi
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 60 Issue: 3 Pages: 156-161

    • DOI

      10.3164/jcbn.16-96

    • NAID

      130005632009

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant

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

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