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Induction of cardiac mesoderm by defined factors

Research Project

Project/Area Number 17H04179
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Cardiovascular medicine
Research InstitutionUniversity of Tsukuba (2018-2019, 2021)
Keio University (2017)

Principal Investigator

Ieda Masaki  筑波大学, 医学医療系, 教授 (70296557)

Co-Investigator(Kenkyū-buntansha) 五島 直樹  国立研究開発法人産業技術総合研究所, 生命工学領域, 招聘研究員 (70215482)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords心臓再生 / リプログラミング / 心臓前駆細胞 / 再生 / 心臓 / 分子心臓学
Outline of Final Research Achievements

Adult hearts have little regenerative capacity. We found that Tbx6 overexpression could induce mesoderm and cardiac progenitor gene expression in fibroblasts. We also found that Tbx6 is critical for mesoderm induction and subsequent lineage diversification from pluripotent stem cells (PSCs). Transient Tbx6 expression induced nascent mesoderm and cardiovascular lineages from mouse and human PSCs, whereas prolonged Tbx6 expression suppressed cardiac differentiation and induced somite lineages, including skeletal muscle and chondrocytes.

Academic Significance and Societal Importance of the Research Achievements

本研究は線維芽細胞を直接心臓前駆細胞に転換して心臓再生する全く新しい概念の研究である。これまで自らが積み上げてきた心筋直接リプログラミング研究の多くの知見や材料を利用するため、他より圧倒的に優位な立場で研究を進められる。線維芽細胞から心臓前駆細胞へのリプログラミングは、他の様々な臓器でも組織幹細胞への直接リプログラミングが可能であることを示しており、心臓再生医療実現への貢献のみならず他領域への大きな波及効果も期待できる。

Report

(4 results)
  • 2021 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (24 results)

All 2022 2021 2020 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 9 results) Presentation (13 results) (of which Int'l Joint Research: 10 results,  Invited: 13 results)

  • [Journal Article] A biomimetic hydrogel culture system to facilitate cardiac reprogramming2022

    • Author(s)
      Kurotsu Shota、Sadahiro Taketaro、Harada Ichiro、Ieda Masaki
    • Journal Title

      STAR Protocols

      Volume: 3 Issue: 1 Pages: 101122-101122

    • DOI

      10.1016/j.xpro.2022.101122

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In vivo reprogramming as a new approach to cardiac regenerative therapy2022

    • Author(s)
      Sadahiro Taketaro、Ieda Masaki
    • Journal Title

      Seminars in Cell & Developmental Biology

      Volume: 122 Pages: 21-27

    • DOI

      10.1016/j.semcdb.2021.06.019

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Overexpression of Gata4, Mef2c, and Tbx5 Generates Induced Cardiomyocytes Via Direct Reprogramming and Rare Fusion in the Heart2021

    • Author(s)
      Isomi Mari、Sadahiro Taketaro、Yamakawa Hiroyuki、Fujita Ryo、Yamada Yu、Abe Yuto、Murakata Yoshiko、Akiyama Tatsuya、Shu Tsugumine、Mizukami Hiroaki、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Circulation

      Volume: 143 Issue: 21 Pages: 2123-2125

    • DOI

      10.1161/circulationaha.120.052799

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Direct reprogramming with Sendai virus vectors repaired infarct hearts at the chronic stage2021

    • Author(s)
      Isomi Mari、Sadahiro Taketaro、Fujita Ryo、Abe Yuto、Yamada Yu、Akiyama Tatsuya、Mizukami Hiroaki、Shu Tsugumine、Fukuda Keiichi、Ieda Masaki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 560 Pages: 87-92

    • DOI

      10.1016/j.bbrc.2021.04.121

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Key Regulators of Cardiovascular Differentiation and Regeneration: Harnessing the Potential of Direct Reprogramming to Treat Heart Failure2020

    • Author(s)
      IEDA MASAKI
    • Journal Title

      Journal of Cardiac Failure

      Volume: 26 Issue: 1 Pages: 80-84

    • DOI

      10.1016/j.cardfail.2019.09.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct Cardiac Reprogramming for Cardiovascular Regeneration and Differentiation2019

    • Author(s)
      Sadahiro Taketaro、Ieda Masaki
    • Journal Title

      The Keio Journal of Medicine

      Volume: - Issue: 3 Pages: 49-58

    • DOI

      10.2302/kjm.2019-0008-oa

    • NAID

      130007907362

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2.Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts.2019

    • Author(s)
      Haginiwa S, Sadahiro T, Kojima H, Isomi M, Tamura F, Kurotsu S, Tani H, Muraoka N, Miyake N, Miyake K, Fukuda K, Ieda M.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 513 Issue: 4 Pages: 1041-1047

    • DOI

      10.1016/j.bbrc.2019.04.087

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Direct In Vivo Reprogramming with Sendai Virus Vectors Improves Cardiac Function after Myocardial Infarction.2018

    • Author(s)
      Miyamoto K, Akiyama M, Tamura F, Isomi M, Yamakawa H, Sadahiro T, Muraoka N, Kojima H, Haginiwa S, Kurotsu S, Tani H, Wang L, Qian L, Inoue M, Ide Y, Kurokawa J, Yamamoto T, Seki T, Aeba R, Yamagishi H, Fukuda K, Ieda M.
    • Journal Title

      Cell Stem Cell.

      Volume: 4 Issue: 1 Pages: 91-103

    • DOI

      10.1016/j.stem.2017.11.010

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distinct expression patterns of Flk1 and Flt1 in the coronary vascular system during development and after myocardial infarction2018

    • Author(s)
      Kurotsu Shota、Osakabe Rina、Isomi Mari、Tamura Fumiya、Sadahiro Taketaro、Muraoka Naoto、Kojima Hidenori、Haginiwa Sho、Tani Hidenori、Nara Kaori、Kubota Yoshiaki、Ema Masatsugu、Fukuda Keiichi、Suzuki Takeshi、Ieda Masaki
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 495 Issue: 1 Pages: 884-891

    • DOI

      10.1016/j.bbrc.2017.11.094

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Direct Reprogramming, Epigenetics, and Cardiac Regeneration2017

    • Author(s)
      Kurotsu Shota、Suzuki Takeshi、Ieda Masaki
    • Journal Title

      J Card Fail.

      Volume: 23 Issue: 7 Pages: 552-557

    • DOI

      10.1016/j.cardfail.2017.05.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Single-Construct Polycistronic Doxycycline-Inducible Vectors Improve Direct Cardiac Reprogramming and Can Be Used to Identify the Critical Timing of Transgene Expression.2017

    • Author(s)
      Umei TC, Yamakawa H, Muraoka N, Sadahiro T, Isomi M, Haginiwa S, Kojima H, Kurotsu S, Tamura F, Osakabe R, Tani H, Nara K, Miyoshi H, Fukuda K, Ieda M.
    • Journal Title

      Int J Mol Sci.

      Volume: 18 Issue: 8 Pages: 1805-1805

    • DOI

      10.3390/ijms18081805

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Cardiac Fibrosis, Reprogramming, and Regeneration2022

    • Author(s)
      家田真樹
    • Organizer
      第86 回日本循環器学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 再生医療の最前線-人間の潜在能力を生かした治療2022

    • Author(s)
      家田真樹
    • Organizer
      武蔵野大学・人間科学研究所シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Cardiac reprogramming and regeneration2021

    • Author(s)
      Masaki Ieda
    • Organizer
      5th International Forum on Medical Innovation of Cell & Bio Therapy
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Converting scar tissue to heart muscle after a heart attack2021

    • Author(s)
      Masaki Ieda
    • Organizer
      2021 Annual Spring Scientific Conference of the Korean Society of Cardiology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 心臓再生医療の現状と展望 ダイレクトリプログラミングによる心臓再生2021

    • Author(s)
      家田真樹
    • Organizer
      第25回日本心不全学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Making New Muscle Cells from Fibroblasts for Heart Regeneration2019

    • Author(s)
      Masaki Ieda
    • Organizer
      The KAST-NAMOK joint International Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct Reprogramming for Cardiovascular Regeneration2019

    • Author(s)
      Masaki Ieda
    • Organizer
      CSSCR annual session
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct reprogramming and cardiovascular research2019

    • Author(s)
      Masaki Ieda
    • Organizer
      AHA BCVS 2019 Scientific Sessions Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct Reprogramming toward Cutting-edge Cardiovascular Research2019

    • Author(s)
      Masaki Ieda
    • Organizer
      Gwangju-International Interventioanl Cardiology Symposium
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct Cardiac Reprogramming and Heart Regeneration2017

    • Author(s)
      Masaki Ieda
    • Organizer
      Yonsei Stem cell and Cardiovascular Regeneration Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechano-transduction and Direct Cardiac Reprogramming for Heart Regeneration2017

    • Author(s)
      Masaki Ieda
    • Organizer
      International symposium on mechanobiology with its cutting edge and diversity
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct Cardiac Reprogramming, Cell Fate Decision, and Heart Regeneration2017

    • Author(s)
      Masaki Ieda
    • Organizer
      The 27th Hot Spring Harbor International Symposium
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct Reprogramming and Cardiac Regeneration2017

    • Author(s)
      Masaki Ieda
    • Organizer
      Cell Press Lab Links「Stem cells」
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited

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Published: 2017-04-28   Modified: 2023-01-30  

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