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Epigenome analysis in cardiomyocyte differentiation and failure

Research Project

Project/Area Number 26253049
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cardiovascular medicine
Research InstitutionThe University of Tokyo

Principal Investigator

Komuro Issei  東京大学, 医学部附属病院, 教授 (30260483)

Co-Investigator(Kenkyū-buntansha) 内藤 篤彦  東京大学, 医学部附属病院, 助教 (10588891)
野村 征太郎  東京大学, 医学部附属病院, 助教 (10722118)
Co-Investigator(Renkei-kenkyūsha) NOMURA Seitaro  東京大学, 医学部附属病院, 特任助教 (10722118)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000)
Fiscal Year 2016: ¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2015: ¥14,430,000 (Direct Cost: ¥11,100,000、Indirect Cost: ¥3,330,000)
Fiscal Year 2014: ¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Keywords分子心臓学 / エピゲノム / 遺伝子制御 / 分子心臓病学 / 転写制御 / 循環器 / ゲノム / 心不全 / 心筋細胞分化
Outline of Final Research Achievements

We analyzed epigenomic regulation of cardiomyocyte differentiation and heart failure. Genome-wide enhancer analysis revealed that β-catenin, which is activated by Wnt signaling upon differentiation, forms a complex with epigenomic regulators to activate mesodermal enhancers and provokes the down-stream gene program. Through integrative analysis of single-cell transcriptomes and epigenomes, we also unveiled that transcription factors which are induced upon pressure overload activates enhancers regulating the heart failure gene program. These results indicate that the epigenome regulates cardiomyocyte differentiation and failure.

Report

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

Research Products

(42 results)

All 2017 2016 2015 2014

All Journal Article (21 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 17 results,  Open Access: 12 results,  Acknowledgement Compliant: 10 results) Presentation (21 results) (of which Int'l Joint Research: 1 results,  Invited: 18 results)

  • [Journal Article] Dysbiosis and compositional alterations with aging in the gut microbiota of patients with heart failure.2017

    • Author(s)
      Kamo T, Akazawa H, Suda W, Saga-Kamo A, Shimizu Y, Yagi H, Liu Q, Nomura S, Naito AT, Takeda N, Harada M, Toko H, Kumagai H, Ikeda Y, Takimoto E, Suzuki JI, Honda K, Morita H, Hattori M, Komuro I.
    • Journal Title

      Plos One.

      Volume: 12 Pages: 0174099-0174099

    • DOI

      10.1371/journal.pone.0174099

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] HIF-1alpha-PDK1 axis-induced active glycolysis plays an essential role in macrophage migratory capacity2017

    • Author(s)
      Semba, H., Takeda, N., Isagawa, T., Sugiura, Y., Honda, K., Wake, M., Miyazawa, H., Yamaguchi, Y., Miura, M., Jenkins, DM., Choi, H., Kim, JW., Asagiri, M., Cowburn, AS., Abe, H., Soma, K., Koyama, K., Katoh, M., Sayama, K., Goda, N., Johnson, RS., Manabe, I., Nagai, R., Komuro, I.
    • Journal Title

      Nat Commun. 2016 May 18;7:11635.

      Volume: 7 Pages: 11635-11635

    • DOI

      10.1038/ncomms11635

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A Strategy for Genomic Research on Common Cardiovascular Diseases Aiming at the Realization of Precision Medicine: Personal Insights and Perspectives.2016

    • Author(s)
      Morita H, Komuro I.
    • Journal Title

      Circ Res.

      Volume: 119 Pages: 900-903

    • DOI

      10.1161/circresaha.116.309802

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fukutin gene mutations that cause left ventricular noncompaction.2016

    • Author(s)
      Amiya E, Morita H, Hatano M, Nitta D, Hosoya Y, Maki H, Motozawa Y, Sato N, Ishiura H, Numakura S, Shintani Y, Kinugawa K, Takeda N, Shimizu J, Tsuji S, Komuro I.
    • Journal Title

      Int J Cardiol

      Volume: 222 Pages: 727-729

    • DOI

      10.1016/j.ijcard.2016.08.011

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel molecular mechanisms and regeneration therapy for heart failure.2016

    • Author(s)
      Oka T, Morita H, Komuro I.
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 92 Pages: 46-51

    • DOI

      10.1016/j.yjmcc.2016.01.028

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation of Induced Pluripotent Stem Cells From Patients With Duchenne Muscular Dystrophy and Their Induction to Cardiomyocytes2016

    • Author(s)
      Hashimoto A, Naito AT, Lee JK, Kitazume-Taneike R, Ito M, Yamaguchi T, Nakata R, Sumida T, Okada K, Nakagawa A, Higo T, Kuramoto Y, Sakai T, Tominaga K, Okinaga T, Kogaki S, Ozono K, Miyagawa S, Sawa Y, Sakata Y, Morita H, Umezawa A, Komuro I.
    • Journal Title

      Int. Heart J.

      Volume: 57 Issue: 1 Pages: 112-117

    • DOI

      10.1536/ihj.15-376

    • NAID

      130005120987

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Higdla is a oositive regulaator of cytochrome c oxidase2015

    • Author(s)
      T. Hayashi, Y. Asano, Y. Shintani, H. Aoyama, H. Kioka, O. Tsukamoto, M. Hikita, K. Shinzawa-Itoh, K. Takajuji, S. Higo, H. Kato, S. Yamazaki, K. Matsuoka, A. Nakano, H. Asanuma, M. Asakura, T. Minamino, Y. Goto, T. Ogura, M. Kitakaze, I. Komuro, Y. Sakata, T. Tsukihara, S. Yoshikawa, S. Takashima
    • Journal Title

      Proc Natl Acad Sci U SA

      Volume: 112 Pages: 1553-1553

    • DOI

      10.1073/pnas.1419767112

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Complement C1q-induced activation of β-catenin signalling causes hypertensive arterial remodelling.2015

    • Author(s)
      Sumida T, Naito AT, Nomura S, Nakagawa A, Higo T, Hashimoto A, Okada K, Sakai T, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Minamino T, Offermanns S, Noda T, Botto M, Kobayashi Y, Morita H, Manabe I, Nagai T, Shiojima I, Komuro I.
    • Journal Title

      Nature Communications

      Volume: 6 Pages: 1-12

    • DOI

      10.1038/ncomms7241

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Wnt/β-Catenin Signaling Contributes to Skeletal Myopathy in Heart Failure via Direct Interaction With Forkhead Box O.2015

    • Author(s)
      Okada K, Naito AT, Higo T, Nakagawa A, Shibamoto M, Sakai T, Hashimoto A, Kuramoto Y, Sumida T, Nomura S, Ito M, Yamaguchi T, Oka T, Akazawa H, Lee JK, Morimoto S, Sakata Y, Shiojima I, Komuro I.
    • Journal Title

      Circ Heart Fail

      Volume: 8 Pages: 799-808

    • DOI

      10.1161/circheartfailure.114.001958

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Monitoring beta-arrestin recruitment via beta-lactamase enzyme fragment complementation: purification of peptide E as a low-affinity ligand for mammalian bombesin receptors2015

    • Author(s)
      Ikeda Y*, Kumagai H*, Okazaki H, Fujishiro M, Motozawa Y, Nomura S, Takeda N, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Komuro I, Yanagisawa M (co-first author)
    • Journal Title

      PLoS One.

      Volume: 10

    • DOI

      10.1371/journal.pone.0127445

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Quantitative measurement of GPCR endocytosis via pulse-chase covalent labeling2015

    • Author(s)
      Kumagai H, Ikeda Y, Motozawa Y, Fujishiro M, Okamura T, Fujio K, Okazaki H, Nomura S, Takeda N, Harada M, Toko H, Takimoto E, Akazawa H, Morita H, Suzuki J, Yamazaki T, Yamamoto K, Komuro I, Yanagisawa M
    • Journal Title

      PLoS One.

      Volume: 10

    • DOI

      10.1371/journal.pone.0129394

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Angiotensin II receptor blockade promotes repair of skeletal muscle through down-regulation of aging-promoting C1q expression.2015

    • Author(s)
      Yabumoto C, Akazawa H, Yamamoto R, Yano M, Kudo-Sakamoto Y, Sumida T, Kamo T, Yagi H, Shimizu Y, Saga-Kamo A, Naito AT, Oka T, Lee JK, Suzuki J, Sakata Y, Uejima E, Komuro I.
    • Journal Title

      Sci Rep.

      Volume: 5 Pages: 14453-14453

    • DOI

      10.1038/srep14453

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD(+) protects the heart against pressure overload.2015

    • Author(s)
      Yano M, Akazawa H, Oka T, Yabumoto C, Kudo-Sakamoto Y, Kamo T, Shimizu Y, Yagi H, Naito AT, Lee JK, Suzuki J, Sakata Y, Komuro I.
    • Journal Title

      Sci Rep.

      Volume: 5 Pages: 15857-15857

    • DOI

      10.1038/srep15857

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 【再生医療-新たな医療を求めて-】 臨床応用を目指した基礎研究 疾患モデル細胞、iPS細胞を用いた毒性評価と創薬研究 iPS細胞を用いた遺伝性心筋疾患の病態解明と治療法開発2015

    • Author(s)
      伊藤 正道、内藤 篤彦、小室 一成
    • Journal Title

      日本臨床

      Volume: 73 Pages: 411-415

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 【疾患特異的iPSの基礎と臨床】 疾患特異的iPSの臨床 循環器疾患における現況2015

    • Author(s)
      伊藤 正道、内藤 篤彦、小室 一成
    • Journal Title

      Surgery Frontier

      Volume: 22 Pages: 137-141

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 【心筋再生の現状と展望】 iPS細胞を用いた拡張型心筋症の病態解析2015

    • Author(s)
      伊藤 正道、内藤 篤彦、小室 一成
    • Journal Title

      最新医学

      Volume: 70 Pages: 1683-1688

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 心不全における心筋細胞の1細胞heterogeneityとその意義2015

    • Author(s)
      野村 征太郎、佐藤 真洋、藤田 隆教、山口 敏弘、住田 智一、内藤 篤彦、東口 治弘、油谷 浩幸、小室 一成
    • Journal Title

      日本内分泌学会雑誌

      Volume: 91 Pages: 636-636

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Anti-inflammatory peptides from cardiac progenitors ameliorate dysfunction after myocardial infarction.2014

    • Author(s)
      Liu ML, Nagai T, Tokunaga M, Iwanaga K, Matsuura K, Takahashi T, Kanda M, Kondo N, Naito AT, Komuro I, Kobayashi Y.
    • Journal Title

      J Am Heart Assoc.

      Volume: 3

    • DOI

      10.1161/jaha.114.001101

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Post-myocardial Infarction Remodeling Is Involved in the Progression of Calpain-dependent Cleavage of N-cadherin2014

    • Author(s)
      Yoko Kudo-Sakamoto, Hiroshi Akazawa, Kaoru Ito, Jiro Takano, Masamichi Yano, Chizuru Yabumoto, Atsuhiko T. Naito, Toru Oka, Jong-Kook Lee, Yasushi Sakata, Jun-ichi Suzuki, Takaomi C. Saido and Issei Komuro
    • Journal Title

      J Biol Chem.

      Volume: 289 Pages: 19408-19

    • DOI

      10.1074/jbc.m114.567206

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Noninvasive and quantitative live imaging reveals a potential stress-responsive enhancer in the failing heart.2014

    • Author(s)
      Matsuoka K, Asano Y, Higo S, Tsukamoto O, Yan Y, Yamazaki S, Matsuzaki T, Kioka H, Kato H, Uno Y, Asakura M, Asanuma H, Minamino T, Aburatani H, Kitakaze M, Komuro I, Takashima S.
    • Journal Title

      FASEB J

      Volume: 28(4) Pages: 1870-1870

    • DOI

      10.1096/fj.13-245522

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Mitochondrial aldehyde dehydrogenase 2 plays protective roles in heart failure after myocardial infarction via suppression of the cytosolic JNK/p53 pathway in mice.2014

    • Author(s)
      Sun A, Zou Y, Wang P, Xu D, Gong H, Wang S, Qin Y, Zhang P, Chen Y, Harada M, Isse T, Kawamoto T, Fan H, Yang P, Akazawa H, Nagai T, Ping P, Komuro I, Ge J.
    • Journal Title

      J Am Heart Assoc.

      Volume: 3

    • DOI

      10.1161/jaha.113.000779

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 臨床・基礎研究の強化2017

    • Author(s)
      小室一成
    • Organizer
      第81回 日本循環器学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-18
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Genetics of Cardiomyopathy2017

    • Author(s)
      野村征太郎
    • Organizer
      第81回 日本循環器学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 若者を心血管病から守る:金沢宣言への提言 Introduction2017

    • Author(s)
      小室一成
    • Organizer
      第81回 日本循環器学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] システム生物学的アプローチによる心不全1細胞モデリング2016

    • Author(s)
      野村征太郎、佐藤真洋、候聡志、藤田隆教、油谷浩幸、小室一成
    • Organizer
      第20回日本心不全学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 心筋症のハイスルーブットな遺伝子解析技術の構築とその応用2016

    • Author(s)
      野村征太郎、飛田尚重、藤田隆教、油谷浩幸、小室一成
    • Organizer
      第20回日本心不全学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-10-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Angiogenesis has two merits heart failure2016

    • Author(s)
      Issei Komuro
    • Organizer
      The 60th Annual Scientific Meeting of The Korean Society of Cardiology 2016
    • Place of Presentation
      Seoul, Korea
    • Year and Date
      2016-09-26
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Inflammation, ageing and heart failure.2016

    • Author(s)
      Issei Komuro
    • Organizer
      ESC Congress 2016
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2016-08-27
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mechanisms for heart failure2016

    • Author(s)
      Issei Komuro
    • Organizer
      World Congress of Cardiology and Cardiovascular Health
    • Place of Presentation
      Mexico City, Mexico
    • Year and Date
      2016-06-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mechanisms of Heart Failure - crosstalks among ischemia, inflammation and senescence-2016

    • Author(s)
      Issei Komuro
    • Organizer
      The 11th IHA International Elite Forum
    • Place of Presentation
      Shanghai, China
    • Year and Date
      2016-05-26
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Plenary Lecture : Molecular Mechanism of Heart Failure2016

    • Author(s)
      Issei Komuro
    • Organizer
      The 4th Wuhan International Conference on Cardiometabolic Science
    • Place of Presentation
      Wuhan, China
    • Year and Date
      2016-05-12
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Cardiac DNA damage causes heart failure.2016

    • Author(s)
      Issei Komuro
    • Organizer
      ISHR XXII World Congress
    • Place of Presentation
      Buenos Aires, Argentina
    • Year and Date
      2016-04-18
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Molecular mechanisms of heart failure2016

    • Author(s)
      Issei Komuro
    • Organizer
      New Frontiers in Cell Death Signaling and Heart Failure
    • Place of Presentation
      ハワイ(アメリカ)
    • Year and Date
      2016-02-19
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 心不全における心筋細胞の1細胞heterogeneityとその意義2015

    • Author(s)
      野村 征太郎、佐藤 真洋、藤田 隆教、山口 敏弘、住田 智一、内藤 篤彦、東口 治弘、油谷 浩幸、小室 一成
    • Organizer
      第19回 日本心血管内分泌代謝学会学術総会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-12-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] 心不全治療と研究の最前線2015

    • Author(s)
      小室一成
    • Organizer
      第114回日本循環器学会 北海道地方会
    • Place of Presentation
      北海道大学学術交流会館(北海道札幌市)
    • Year and Date
      2015-11-28
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Science Highlights From the Japanese Circulation Society2015

    • Author(s)
      Issei Komuro
    • Organizer
      American Heart Association Scientific Sessions 2015
    • Place of Presentation
      オーランド(アメリカ)
    • Year and Date
      2015-11-07
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 心不全の先制医療を目指して2015

    • Author(s)
      小室一成
    • Organizer
      第29回日本医学会総会
    • Place of Presentation
      国立京都国際会館(京都府京都市)
    • Year and Date
      2015-04-11
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Epigenomic switch by Wnt/b-catenin signaling directs cardiomyocyte differentiation2015

    • Author(s)
      Seitaro Nomura, Takanori Fujita, Atsuhiko T. Naito, Hiroyuki Aburatani, and Issei Komuro
    • Organizer
      Keystone Symposia 2015 Heart Disease and Regeneration
    • Place of Presentation
      Copper Mountain, Colorado
    • Year and Date
      2015-03-01 – 2015-03-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] Epigenomic switch by Wnt/b-catenin signaling directs cardiomyocyte differentiation2014

    • Author(s)
      Seitaro Nomura, Takanori Fujita, Atsuhiko T. Naito, Hiroyuki Aburatani, and Issei Komuro
    • Organizer
      American Heart Association Scientific Sessions 2014
    • Place of Presentation
      Chicago
    • Year and Date
      2014-11-16 – 2014-11-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular Mechanisms of Heart Failure2014

    • Author(s)
      Issei Komuro
    • Organizer
      The 12th China Congress of ISHR
    • Place of Presentation
      China
    • Year and Date
      2014-08-15
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] PI3 Kinase signaling and heart failure2014

    • Author(s)
      Issei Komuro
    • Organizer
      Heart Failure 2014
    • Place of Presentation
      Greece
    • Year and Date
      2014-05-19
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 心不全の新しい治療2014

    • Author(s)
      小室一成
    • Organizer
      日本麻酔科学会第61回学術集会
    • Place of Presentation
      神奈川
    • Year and Date
      2014-05-16
    • Related Report
      2014 Annual Research Report
    • Invited

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Published: 2014-04-04   Modified: 2018-03-22  

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