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Analysis of regulating mechanism for development and differentiation of special cardiomyocytes

Research Project

Project/Area Number 16K08443
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionHiroshima University

Principal Investigator

Hiroki Kokubo  広島大学, 医歯薬保健学研究科(医), 講師 (10270480)

Co-Investigator(Kenkyū-buntansha) 吉栖 正生  広島大学, 医歯薬保健学研究科(医), 教授 (20282626)
Research Collaborator Saga Yumiko  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords心筋 / 刺激伝導系 / 特殊心筋
Outline of Final Research Achievements

Understanding of the molecular mechanism of cadiomyocytes differentiation, how the heart progenitor cells differentiate into the working myocardium consisting atria and ventircles, and also into special myocardium constituting sinus venous, including the sinoatrial node controlling heartbeat, has an important key role in the development of the regenerative medicine technology. In this study, we have examined how this progenitor cells are regulated to differentiate into two working and special myocardium, mainly on the role of the BMP signal, in order to elucidate molecular mechanism of the myocardium differentiation by focusing our newly identified heart progenitor cell population to contribute to the left ventricle, the atria, and the sinus venous, and clarified a new mechanism for myocardium differentiation.

Academic Significance and Societal Importance of the Research Achievements

循環器領域は、iPS細胞より誘導分化させた固有心筋の細胞シートを心不全患者に直接移植する治療法が治験に入るなど、再生医療が実用段階に入っている。しかしながら、心筋前駆細胞が如何にして固有並びに特殊心筋へと分化するのか、その分子メカニズムは分かっていない。本研究によって、Bmpの心筋制御の新たな分子機構を明らかにできたことは、大きな学術的意義を持つと考えられる。この知見を基に、iPSやES細胞から固有心筋や特殊心筋を効率的に分化誘導する方法へと結び着くことが期待され、大きな社会的意義を持つと考えている。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (26 results)

All 2019 2018 2017 2016 Other

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 2 results) Presentation (14 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results) Remarks (6 results)

  • [Journal Article] Cell-autonomous and redundant roles of Hey1 and HeyL in muscle stem cells: HeyL requires Hes1 to bind diverse DNA sites2019

    • Author(s)
      Noguchi Yu-taro、Nakamura Miki、Hino Nobumasa、Nogami Jumpei、Tsuji Sayaka、Sato Takahiko、Zhang Lidan、Tsujikawa Kazutake、Tanaka Toru、Izawa Kohei、Okada Yoshiaki、Doi Takefumi、Kokubo Hiroki、Harada Akihito、Uezumi Akiyoshi、Gessler Manfred、Ohkawa Yasuyuki、Fukada So-ichiro
    • Journal Title

      Development

      Volume: 146 Issue: 4 Pages: 163618-163618

    • DOI

      10.1242/dev.163618

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The SGLT2 Inhibitor Luseogliflozin Rapidly Normalizes Aortic mRNA Levels of Inflammation-Related but Not Lipid-Metabolism-Related Genes and Suppresses Atherosclerosis in Diabetic ApoE KO Mice.2017

    • Author(s)
      Yusuke Nakatsu, Hiroki Kokubo, Batmunkh Bumdelger, Masao Yoshizumi, Takeshi Yamamotoya, Yasuka Matsunaga, Koji Ueda, Yuki Inoue, Masa-Ki Inoue, Midori Fujishiro, Akifumi Kushiyama, Hiraku Ono, Hideyuki Sakoda, and Tomoichiro Asano
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 18(8) Issue: 8 Pages: 1704-1717

    • DOI

      10.3390/ijms18081704

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sfrp5 identifies murine cardiac progenitors for all myocardial structures except for the right ventricle.2017

    • Author(s)
      Fujii, M., Sakaguchi, A., Kamata, R., Nagao, M., Kikuchi, Y., Evans, S.M., Yoshizumi M., Shimono, A., Saga, Y., and Kokubo, H.
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 14664-14664

    • DOI

      10.1038/ncomms14664

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] EPA Prevents the Development of Abdominal Aortic Aneurysms through Gpr-120/Ffar-4.2016

    • Author(s)
      Kamata R, Bumdelger B, Kokubo H, Fujii M, Yoshimura K, Ishida T, Ishida M, Yoshizumi M.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 10 Pages: 0165132-0165146

    • DOI

      10.1371/journal.pone.0165132

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transcriptomic analyses of Hand2 transgenic embryos.2016

    • Author(s)
      Funato N, Kokubo H, Saga Y.
    • Journal Title

      Genom Data.

      Volume: 9 Pages: 60-62

    • DOI

      10.1016/j.gdata.2016.06.015

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Specification of jaw identity by the Hand2 transcription factor.2016

    • Author(s)
      Funato N, Kokubo H, Nakamura M, Yanagisawa H, Saga Y.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 28405-28405

    • DOI

      10.1038/srep28405

    • NAID

      120007135331

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 心臓における刺激伝導系前駆細胞の系譜解析2019

    • Author(s)
      坂口あかね、小久保博樹、安島理恵子、相賀裕美子
    • Organizer
      第124回日本解剖学会総会 シンポジウム “血管研究のイノベーション:構成細胞の起源と形成メカニズムを考える”
    • Related Report
      2018 Annual Research Report
  • [Presentation] 心臓前駆細胞から見た心臓形成 ― 冠状動静脈から刺激伝導系まで2018

    • Author(s)
      小久保博樹、吉栖 正生
    • Organizer
      第 59 回日本脈管学会総会 シンポジウム「発生学から見た心肺・血管・リンパ管学」
    • Related Report
      2018 Annual Research Report
  • [Presentation] EPAはJNKシグナル伝達経路の制御を通して腹部大動脈瘤の増悪を抑制する2018

    • Author(s)
      唐崎航平、Batmunkh Bumdelger、小久保博樹、吉栖正生
    • Organizer
      第 59 回日本脈管学会総会
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 心臓における刺激伝導系前駆細胞の系譜解析2018

    • Author(s)
      坂口あかね、小久保博樹、安島理恵子、相賀裕美子
    • Organizer
      第72回日本解剖学会中国・四国支部学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Fate mapping of two types of cardiac progenitor cells2018

    • Author(s)
      Hiroki Kokubo, Masayuki Fuiji, and Masao Yoshizumi
    • Organizer
      Weinstein Cardiovascular development and regeneration conference
    • Related Report
      2018 Annual Research Report
  • [Presentation] Identification of cardiac progenitors for all cardial structure except for the Right ventricle2017

    • Author(s)
      Masayuki Fujii, Akane Sakaguchi, Masao Yoshizumi, Yumiko Saga, Hiroki Kokubo
    • Organizer
      日本解剖学会
    • Place of Presentation
      長崎
    • Year and Date
      2017-03-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Identification of cardiac progenitors for the outflow tract, the left ventricle, atria, and the sinus venosus2017

    • Author(s)
      Masayuki Fujii, Akane Sakaguchi, Masao Yoshizumi, Yumiko Saga, Hiroki Kokubo
    • Organizer
      日本循環器学会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] EPA attenuates the progression of Abdominal Aortic Aneurysms2017

    • Author(s)
      Ryo Kamata、Hiroki Kokubo、Batmunkh Bumdelger、Masao Yoshizumi
    • Organizer
      日本循環器学会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 右心室以外の心筋へと寄与する新たな心筋前駆細胞の同定2017

    • Author(s)
      藤井雅行、吉栖正生、小久保博樹
    • Organizer
      小児循環器学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Osteoprotegerin prevents from aortic aneurysm development2017

    • Author(s)
      Bumdelger Batmunkh, Hiroki Kokubo, Masao Yoshizumi
    • Organizer
      動脈硬化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Novel cardiac progenitors for all components of the heart except for the right ventricle2017

    • Author(s)
      Hiroki Kokubo, Masayuki Fujii, Akane Sakaguchi, Yumiko Saga, Masao Yoshizumi
    • Organizer
      Takao Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of cardiac progenitors for the outflow tract, the left ventricle, the atria, and the sinus venosus2017

    • Author(s)
      Hiroki Kokubo, Masayuki Fujii, Akane Sakaguchi, Yumiko Saga, Masao Yoshizumi
    • Organizer
      分子生物学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 右心室以外に寄与する新たな心臓前駆細胞の同定2017

    • Author(s)
      小久保博樹
    • Organizer
      CVMW2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] EPAは腹部大動脈瘤を抑制する2016

    • Author(s)
      鎌田諒、小久保博樹、Batmunkh Bumdelger、吉栖正生
    • Organizer
      日本脈管学会
    • Place of Presentation
      奈良
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Remarks] 【研究成果】右心室以外の心臓を構成する細胞へ分化する前駆細胞を発見

    • URL

      https://www.hiroshima-u.ac.jp/news/38570

    • Related Report
      2018 Annual Research Report
  • [Remarks] 右心室以外の心臓を構成する細胞へ分化する前駆細胞を発見

    • URL

      https://www.hiroshima-u.ac.jp/system/files/89898/BHS_NEWS_Vol12_7.pdf

    • Related Report
      2017 Research-status Report
  • [Remarks] Precursor cells for all components of the heart

    • URL

      https://www.hiroshima-u.ac.jp/en/news/43350

    • Related Report
      2017 Research-status Report
  • [Remarks] 右心室以外の心臓を構成する細胞へ分化する前駆細胞を発見

    • URL

      https://www.hiroshima-u.ac.jp/news/38570

    • Related Report
      2016 Research-status Report
  • [Remarks] 右心室以外の心臓を構成する細胞へ分化する前駆細胞を発見

    • URL

      https://www.nig.ac.jp/nig/ja/2017/03/research-highlights_ja/20170321.html

    • Related Report
      2016 Research-status Report
  • [Remarks] Nature communications 誌掲載

    • URL

      http://home.hiroshima-u.ac.jp/seiri1/topics/detail.html?CN=197447

    • Related Report
      2016 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2022-01-27  

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