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Cardiac reprogramming and miRNA

Research Project

Project/Area Number 26293193
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKeio University

Principal Investigator

Ieda Masaki  慶應義塾大学, 医学部(信濃町), 講師 (70296557)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords再生 / リプログラミング / マイクロRNA / 再生医学 / 循環器・高血圧 / 心筋 / miR
Outline of Final Research Achievements

Here we found that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated 7-fold more beating iCMs from mouse embryonic fibroblasts, and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report

Research Products

(47 results)

All 2018 2017 2016 2015

All Journal Article (12 results) (of which Int'l Joint Research: 10 results,  Peer Reviewed: 12 results,  Open Access: 7 results,  Acknowledgement Compliant: 5 results) Presentation (20 results) (of which Int'l Joint Research: 12 results,  Invited: 20 results) Book (14 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [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 Pages: 91-103

    • DOI

      10.1016/j.stem.2017.11.010

    • Related Report
      2017 Annual Research Report 2016 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 Pages: 884-891

    • DOI

      10.1016/j.bbrc.2017.11.094

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / 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 Pages: 1805-1805

    • DOI

      10.3390/ijms18081805

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Placental labyrinth formation in mice requires endothelial FLRT2/UNC5B signaling2017

    • Author(s)
      Tai-Nagara Ikue、Yoshikawa Yusuke、Numata Naoko、Ando Tomofumi、Okabe Keisuke、Sugiura Yuki、Ieda Masaki、Takakura Nobuyuki、Nakagawa Osamu、Zhou Bin、Okabayashi Koji、Suematsu Makoto、Kitagawa Yuko、Bastmeyer Martin、Sato Kohji、Klein R?diger、Navankasattusas Sutip、Li Dean Y.、Yamagishi Satoru、Kubota Yoshiaki
    • Journal Title

      Development.

      Volume: 144 Pages: 2392-2401

    • DOI

      10.1242/dev.149757

    • Related Report
      2017 Annual Research Report 2016 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

      Journal of Cardiac Failure

      Volume: 23 Pages: 552-557

    • DOI

      10.1016/j.cardfail.2017.05.009

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Discovery and progress of direct cardiac reprogramming.2017

    • Author(s)
      Kojima H, Ieda M
    • Journal Title

      Cell Mol Life Sci.

      Volume: 1 Pages: 1-13

    • DOI

      10.1007/s00018-017-2466-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure2017

    • Author(s)
      Ono T, Kamimura N, Matsuhashi T, Nagai T, Nishiyama T, Endo J, Hishiki T, Nakanishi T, Shimizu N, Tanaka H, Ohta S, Suematsu M, Ieda M, Sano M, Fukuda K, Kaneda R
    • Journal Title

      Scientific Reports

      Volume: 7 Pages: 39752-39752

    • DOI

      10.1038/srep39752

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Heart Development, Diseases, and Regeneration – New Approaches From Innervation, Fibroblasts, and Reprogramming –2016

    • Author(s)
      Ieda M
    • Journal Title

      Circ J

      Volume: 80 Issue: 10 Pages: 2081-2088

    • DOI

      10.1253/circj.cj-16-0815

      10.1253/circj.CJ-16-0815

    • NAID

      130005419072

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Effective Cibenzoline Treatment in a Patient With Midventricular Obstruction After Transcatheter Aortic Valve Implantation.2016

    • Author(s)
      Isobe S, Ieda M, Kohno T, Nishiyama T, Maekawa Y, Tsuruta H, Murata M, Yashima F, Yanagisawa R, Tanaka M, Inami S, Nasuno T, Haruyama A, Sano M, Hayashida K, Fukuda K.
    • Journal Title

      Circulation Heart Failure

      Volume: 9

    • DOI

      10.1161/circheartfailure.115.002629

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Neural crest-derived resident cardiac cells contribute to the restoration of adrenergic function of transplanted heart in rodent.2016

    • Author(s)
      Tamura Y, Sano M, Nakamura H, Ito K, Sato Y, Shinmura K, Ieda M, Fujita J, Kurosawa H, Ogawa S, Nakano S, Matsuzaki M, Fukuda K.
    • Journal Title

      Cardiovasc Res.

      Volume: 109 Pages: 350-357

    • DOI

      10.1093/cvr/cvv267

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Strategies for heart regeneration: approaches ranging from induced pluripotent stem cells to direct cardiac reprogramming.2015

    • Author(s)
      Yamakawa H, Ieda M.
    • Journal Title

      Stem Cell Rep

      Volume: 56 Pages: 1128-1142

    • DOI

      10.1016/j.stemcr.2015.10.019

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Direct Cardiac Reprogramming: Progress and Challenges in Basic Biology and Clinical Applications.2015

    • Author(s)
      Sadahiro T, Yamanaka S, Ieda M.
    • Journal Title

      Circ Res.

      Volume: 116 Pages: 1378-1391

    • DOI

      10.1161/circresaha.116.305374

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Direct Cardiac Reprogramming for Heart Regeneration2017

    • Author(s)
      家田真樹
    • Organizer
      CVIT
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 心筋リプログラミングによる新しい心臓再生法の開発2017

    • Author(s)
      家田真樹
    • Organizer
      第三回日本筋学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 心筋リプログラミングによる心臓再生と心不全治療2017

    • Author(s)
      家田真樹
    • Organizer
      第21回日本心不全学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 線維芽細胞からの直接的心筋細胞作成と心臓再生2017

    • Author(s)
      家田真樹
    • Organizer
      Scientific Exchange Meeting in Chiba
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Direct Cardiac Reprogramming, Regeneration, and Heart Failure2017

    • Author(s)
      家田真樹
    • Organizer
      第82回日本循環器学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Direct Cardiac Reprogramming and Heart Regeneration2017

    • Author(s)
      Masaki Ieda
    • Organizer
      Yonsei Stem cell and Cardiovascular Regeneration Symposium 2017
    • Related Report
      2016 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
      2016 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
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct Reprogramming and Cardiac Regeneration2017

    • Author(s)
      Masaki Ieda
    • Organizer
      Cell Press Lab Links
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cardiac Reprogramming and Heart Regeneration via Mechano-Transduction2017

    • Author(s)
      Masaki Ieda
    • Organizer
      3rd International symposium on mechanobiology
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Induced Pluripotent Stem Cells and Direct Cardiac Reprogramming; Solving Barriers for a Powerful Future2016

    • Author(s)
      Masaki Ieda
    • Organizer
      American College of Cardiology: New York Cardiovascular Symposium
    • Place of Presentation
      New York, USA
    • Year and Date
      2016-12-09
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular Mechanisms of Cardiac Reprogramming2016

    • Author(s)
      Masaki Ieda
    • Organizer
      American Heart Association Scientific Sessions 2016
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2016-11-12
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Making New Cardiomyocytes by Direct Reprogramming2016

    • Author(s)
      Masaki Ieda
    • Organizer
      The 5th Gwangju-Boston Joint Cardiology Symposium
    • Place of Presentation
      Gwangju, South Korea
    • Year and Date
      2016-05-20
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Direct cardiac reprogramming and cell fate decision2016

    • Author(s)
      Masaki Ieda
    • Organizer
      Cardiovascular Development and Regeneration Symposium
    • Place of Presentation
      San Francisco, USA
    • Year and Date
      2016-05-13
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Converting fibroblasts into cardiomyocytes2016

    • Author(s)
      Masaki Ieda
    • Organizer
      2016 ISHR World Congress Symposium
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2016-04-18
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ダイレクトリプログラミングによる心筋再生2016

    • Author(s)
      家田真樹
    • Organizer
      第15回日本再生医療学会シンポジウム
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 心筋直接リプログラミング制御因子の同定と応用2015

    • Author(s)
      家田真樹
    • Organizer
      第38回日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Direct Cardiac Reprogramming for Heart Repair2015

    • Author(s)
      Masaki Ieda
    • Organizer
      9th International Cell Therapy Conference
    • Place of Presentation
      Seoul, South Korea
    • Year and Date
      2015-10-23
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Reprogramming of Cardiac fibroblasts2015

    • Author(s)
      Masaki Ieda
    • Organizer
      American Heart Association Basic Cardiovascular Sciences 2015
    • Place of Presentation
      New Orleans, LA, USA.
    • Year and Date
      2015-07-13
    • Related Report
      2014 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 心筋直接リプログラミングによる心不全治療2015

    • Author(s)
      家田真樹
    • Organizer
      第79回日本循環器学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2015-04-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Book] メカニカルに注目した新しい心臓再生医療の可能性2017

    • Author(s)
      村岡直人、家田真樹
    • Publisher
      医薬ジャーナル
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Book] 心臓の発生・再生・創生2017

    • Author(s)
      谷英典、家田真樹
    • Publisher
      生体の科学
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Book] レジデント2017

    • Author(s)
      家田真樹
    • Publisher
      医学出版
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Book] 創薬・治療のターゲットとしての細胞分化2017

    • Author(s)
      刑部里奈、鈴木岳之、家田真樹
    • Publisher
      日薬理誌
    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
  • [Book] 再生医療―ダイレクトリプログラミング2016

    • Author(s)
      九石優樹、家田真樹
    • Publisher
      日本臨床社
    • Related Report
      2015 Annual Research Report
  • [Book] 循環器専門医2016

    • Author(s)
      田村文弥、家田真樹
    • Publisher
      株式会社南江堂
    • Related Report
      2015 Annual Research Report
  • [Book] 心臓2016

    • Author(s)
      貞廣威太郎、家田真樹
    • Publisher
      株式会社日本医学出版
    • Related Report
      2015 Annual Research Report
  • [Book] Clinical Calcium2016

    • Author(s)
      黒津祥太、家田真樹
    • Publisher
      株式会社医薬ジャーナル
    • Related Report
      2015 Annual Research Report
  • [Book] 細胞2016

    • Author(s)
      山川裕之、家田真樹
    • Publisher
      株式会社ニューサイエンス
    • Related Report
      2015 Annual Research Report
  • [Book] A diversity of emerging physiological and pathological activities2015

    • Author(s)
      Masaki Ieda
    • Publisher
      Springer
    • Related Report
      2014 Annual Research Report
  • [Book] 心筋直接リプログラミングによる新しい心臓再生法の開発2015

    • Author(s)
      家田真樹
    • Publisher
      最新医学
    • Related Report
      2014 Annual Research Report
  • [Book] ダイレクトリプログラミング 線維芽細胞から心筋細胞2015

    • Author(s)
      家田真樹
    • Publisher
      秀潤社
    • Related Report
      2014 Annual Research Report
  • [Book] iCM細胞の樹立と臨床応用への展望2015

    • Author(s)
      家田真樹
    • Publisher
      Heart View
    • Related Report
      2014 Annual Research Report
  • [Book] iPS細胞と心筋直接リプログラミングによる心臓再生医療2015

    • Author(s)
      村岡直人、家田真樹
    • Publisher
      Heart View
    • Related Report
      2014 Annual Research Report
  • [Patent(Industrial Property Rights)] 心筋様細胞の作製方法及びそれに用いる心筋様細胞の作製用組成物2015

    • Inventor(s)
      井上 誠、弘中 孝史、宮本和享、家田真樹
    • Industrial Property Rights Holder
      井上 誠、弘中 孝史、宮本和享、家田真樹
    • Industrial Property Rights Type
      特許
    • Filing Date
      2015-09-30
    • Related Report
      2014 Annual Research Report
    • Overseas

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Published: 2014-04-04   Modified: 2019-03-29  

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