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Fate determination and function acquisition during induction/regeneration of photoreceptors from human somatic cells

Research Project

Project/Area Number 25670741
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionNational Rehabilitation Center for Persons with Disabilities

Principal Investigator

SEKO YUKO  国立障害者リハビリテーションセンター(研究所), 研究所 感覚機能系障害研究部, 室長 (60301157)

Co-Investigator(Kenkyū-buntansha) AZUMA Noriyuki  独立行政法人国立成育医療研究センター, 病院眼科・研究所 視覚科学研究室, 室長 (10159395)
UMEZAWA Akihiro  独立行政法人国立成育医療研究センター, 再生医療センター, センター長 (70213486)
Co-Investigator(Renkei-kenkyūsha) KANEDA Makoto  日本医科大学, 医学系研究科 システム生理学, 教授 (30214480)
Research Collaborator Komuta Yukari  
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords眼発生 / 再生医学 / 網膜視細胞 / 直接的分化誘導 / 杆体 / 錐体 / ダイレクト・リプログラミング / 皮膚線維芽細胞 / 転写因子 / 誘導視細胞 / 光応答 / 網膜再生
Outline of Final Research Achievements

Direct reprogramming is a promising, simple, low-cost approach to generate target cells from somatic cells without using induced pluripotent stem cells. We generated photosensitive photoreceptor-like cells from human iris cells, human dermal fibroblasts and peripheral blood mononuclear cells (PBMCs) by transduction of photoreceptor-related transcription factors (CRX & RAX & OTX2 & NeuroD) via retrovirus vectors and Sendai virus vectors. We found that retinal disease-related genes were efficiently detected in CRX-transduced PBMCs. To improve differentiation levels, we made differentiation conditions close to the in vivo retinal development, such as the expression order of transcription factors and cooperation with retinal pigment epithelium. These modifications facilitated the differentiation of human PBMCs into photoreceptor-like cells. Our induced photoreceptor-like cells might contribute to individualized drug screening and disease modeling of inherited retinal degeneration.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (13 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] In vitro transdifferentiation of human peripheral blood mononuclear cells to photoreceptor-like cells.2016

    • Author(s)
      Komuta Y, Ishii T, Kaneda M, Ueda Y, Miyamoto K, Toyoda M, Umezawa A, Seko Y
    • Journal Title

      Biology Open

      Volume: May 11 Issue: 6 Pages: 709-719

    • DOI

      10.1242/bio.016477

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Notch inhibition allows oncogene-independent generation of iPS cells2015

    • Author(s)
      Ichida JK, T C W J, Williams LA, Carter AC, Shi Y, Moura MT, Ziller M, Singh S, Amabile G, Bock C, Umezawa A, Rubin LL, Bradner JE, Akutsu H, Meissner A, Eggan K
    • Journal Title

      Nature Chemical Biology

      Volume: 1 Issue: 8 Pages: 632-639

    • DOI

      10.1038/nchembio.1552

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ataxia telangiectasia derived iPS cells show preserved x-ray sensitivity and decreased chromosomal instability2014

    • Author(s)
      Fukawatase Y, Toyoda M, Okamura K, Nakamura K, Nakabayashi K, Takada S, Yamazaki-Inoue M, Masuda A, Nasu M, Hata K, Hanaoka K, Higuchi A, Takubo K, Umezawa A
    • Journal Title

      Sci. Rep.

      Volume: 4 Issue: 1 Pages: 5421-5421

    • DOI

      10.1038/srep05421

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Derivation of human differential photoreceptor cells from adult human dermal fibroblasts by defined combinations of CRX, RAX, OTX2 and NEUROD2014

    • Author(s)
      Seko Y, Azuma N, Ishii T, Komuta Y, Miyamoto K, Miyagawa Y, Kaneda M, Umezawa A
    • Journal Title

      Gene to Cells Epub

      Volume: 19(3) Issue: 3 Pages: 198-208

    • DOI

      10.1111/gtc.12127

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Generation and analysis of induced photoreceptor-like cells from fibroblasts of patients2016

    • Author(s)
      Seko Y
    • Organizer
      XXII Biennial Meeting of the International Society for Eye Research - ISER -
    • Place of Presentation
      東京
    • Year and Date
      2016-09-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 網膜リプログラミング研究の進展2016

    • Author(s)
      世古裕子
    • Organizer
      第15回再生医療学会総会 シンポジウム10「幹細胞・リプログラミング研究の新展開」
    • Place of Presentation
      大阪
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] ヒト体細胞から網膜視細胞へのダイレクトリプログラミング2015

    • Author(s)
      世古裕子
    • Organizer
      感覚器セミナー
    • Place of Presentation
      東京
    • Year and Date
      2015-12-15
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 末梢血単核細胞から網膜視細胞様細胞への直接的分化誘導2015

    • Author(s)
      小牟田 縁、石井 俊行、金田 誠、上田 泰次、豊田 雅士、梅澤 明弘、世古 裕子
    • Organizer
      第38回 日本分子生物学会・第88回 日本生化学会
    • Place of Presentation
      神戸
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ヒト培養誘導網膜視細胞の光応答について2014

    • Author(s)
      世古裕子、東範行、石井俊行、小牟田縁、金田誠、梅澤明弘
    • Organizer
      第17回視覚科学フォーラム研究会
    • Place of Presentation
      前橋工科大学、群馬
    • Year and Date
      2014-08-18
    • Related Report
      2014 Research-status Report
  • [Presentation] Direct reprogramming法を用いた視細胞の再生医学2014

    • Author(s)
      世古裕子
    • Organizer
      第245回生理学東京談話会
    • Place of Presentation
      日本医科大学 橘桜会館、東京
    • Year and Date
      2014-07-04
    • Related Report
      2014 Research-status Report
  • [Presentation] Derivation of human differential photoreceptor-like cells from iris cells by defined combinations of transcription factors2014

    • Author(s)
      Seko Y, Azuma N, Kaneda M, Nakatani K, Umezawa A
    • Organizer
      World Ophthalmology Congress 2014
    • Place of Presentation
      東京国際フォーラム、東京
    • Year and Date
      2014-04-05
    • Related Report
      2014 Research-status Report
  • [Presentation] 網膜シグナル制御による眼軸延長抑制の可能性2014

    • Author(s)
      世古裕子
    • Organizer
      第118回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム、東京
    • Year and Date
      2014-04-04
    • Related Report
      2014 Research-status Report
  • [Book] 線維芽細胞 → 視細胞、 細胞工学 別冊ハンドブック ダイレクトリプログラミング2015

    • Author(s)
      世古裕子、梅澤明弘
    • Total Pages
      9
    • Publisher
      秀潤社
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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