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Direct reprogramming of human fibroblasts into hematopoietic cells mainly using ETV2

Research Project

Project/Area Number 26670470
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKeio University

Principal Investigator

Morita Rimpei  慶應義塾大学, 医学部, 准教授 (00362541)

Co-Investigator(Renkei-kenkyūsha) YOSHIMURA Akihiko  慶應義塾大学, 医学部, 教授 (90182815)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords造血幹細胞 / 転写因子 / エピジェネティクス / 血管内皮細胞 / リンパ球
Outline of Final Research Achievements

An ETS family transcription factor ETV2 is essential for hemato-endothelial development in embryo. We have reported that human adult skin fibroblasts directly convert into functional endothelial cells by transducing ETV2.
Interestingly we found that ETV2-transduced human adult skin fibroblasts also expressed RUNX1, TAL1, and GATA2, which were transcription factors essential for hematopoiesis. Thus to generate hematopoietic cells from fibroblasts, we transduced not only ETV2 but also 20 kinds of transcription factors essential for hematopoiesis into human adult skin fibroblasts, then co-cultured them with OP9 stroma cells in the presence of SCF, FLT3L, TPO, IL-3, and IL-6 for four weeks. Consequently we detected CD45+c-Kit+ hematopoietic-like cells by FACS analysis. Our results may leads to generation of functional hematopoietic cells from individual skin in the future.

Report

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

    (6 results)

All 2016 2015

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

  • [Journal Article] ETS transcription factor ETV2 directly converts human fibroblasts into functional endothelial cells.2015

    • Author(s)
      Morita R, Suzuki M, Kasahara H, Shimizu N, Shichita T, Sekiya T, Kimura A, Sasaki K, Yasukawa H, Yoshimura A.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 112 Issue: 1 Pages: 160-165

    • DOI

      10.1073/pnas.1413234112

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Suppression of Th2 and Tfh immune reactions by Nr4a receptors in mature T reg cells2015

    • Author(s)
      Sekiya T, Kondo T, Shichita T, Morita R, Ichinose H, Yoshimura A
    • Journal Title

      J Exp Med.

      Volume: 212 Issue: 10 Pages: 1623-1640

    • DOI

      10.1084/jem.20142088

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] T細胞の免疫リプログラミング2016

    • Author(s)
      吉村昭彦、近藤泰介、染谷和江、岡田匡央、森田林平
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場 (大阪府大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] 細胞工学別冊 ダイレクトリプログラミング2015

    • Author(s)
      森田林平、笠原秀範、吉村昭彦
    • Total Pages
      119
    • Publisher
      秀潤社
    • Related Report
      2015 Annual Research Report
  • [Book] 日本臨牀増刊号 再生医療2015

    • Author(s)
      森田林平、笠原秀範、吉村昭彦
    • Total Pages
      584
    • Publisher
      日本臨牀社
    • Related Report
      2015 Annual Research Report
  • [Book] ダイレクトリプログラミング (第3章 線維芽細胞→血管内皮細胞)2015

    • Author(s)
      森田林平、笠原秀範、吉村昭彦
    • Total Pages
      11
    • Publisher
      秀潤社
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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