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Understanding the functional mechanisms of cardiac cell induction

Research Project

Project/Area Number 22689026
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

TAKEUCHI Jun  東京大学, 分子細胞生物学研究所, 准教授 (10451999)

Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥20,800,000 (Direct Cost: ¥16,000,000、Indirect Cost: ¥4,800,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2010: ¥15,470,000 (Direct Cost: ¥11,900,000、Indirect Cost: ¥3,570,000)
Keywords心筋分化 / 心臓前駆細胞 / エピジェネティクス / クロマチン因子
Research Abstract

Two types of cardiomyocytes; atria-ventricular cardiomyocytes are formed from their common progenitor cell lineages, but a key factor for induction of cardiac progenitor cells as well as the specification of cardiomyocytes is not known yet. To understand atria-ventricular cardiomyocyte or cardiac progenitor specification, we generated gene profiles from aMHC-GFP positive heart cells in these mice lines or Islet1/Flk positive cells in miceembryos. 6 genes were isolated as candidate factors for specification of atria-ventricular cardiomyocytes, 8 genes were screened out as cardiac progenitor specific-genes. Two genes, C or D, were expressed in undifferentiated cell region that defined by islet1/Nkx2-5 gene as major cardiac progenitor markers during development but not expressed in the heart forming region. These genes’ knockout mice exhibit severe defect of OFT and RV and die at approximately E9.5, suggesting that C/D-derived cells contribute to the heart and are essential for cardiogenesis. By using tamoxifen inducible creERT2-ROSA-YFP reporter system, lineage-tracing analysis of C/D-derived cells could easily demonstrated in vivo. In these analyses showed us that previously expressed these genes substantially contribute to the whole-heart in development, expressing in atria/ventricular cardiomyocytes, endothelial cells, smooth muscle, and conduction cells including pacemaker cells. In conclusion, re-expression of C/D as candidate genes is necessary to promote cardiac program in postnatal stages, suggesting that C/D genes play as key regulators to trigger cardiacprogram.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (65 results)

All 2012 2011 2010 Other

All Journal Article (13 results) (of which Peer Reviewed: 4 results) Presentation (43 results) (of which Invited: 5 results) Book (3 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] エピジェネティクスで組織可塑2012

    • Author(s)
      竹内純
    • Journal Title

      実験医学

      Volume: Vol.30 No.18 Pages: 2896-2901

    • Related Report
      2012 Final Research Report
  • [Journal Article] 心臓発生と心疾患のエピジェネティクス-クロマチンモデリング因子・ヒストン修飾因子が織 りなす複雑な臓器発生機構のモデルとして-2012

    • Author(s)
      中村遼、塚原由布子、竹内純
    • Journal Title

      実験医学

      Volume: Vol.30 No.18 Pages: 2923-2931

    • Related Report
      2012 Final Research Report
  • [Journal Article] 心臓発生とその分子メカニズム2012

    • Author(s)
      森田唯加、小柴和子、竹内純
    • Journal Title

      血管医学

      Volume: Vol.13 No.3 Pages: 97-113

    • Related Report
      2012 Final Research Report
  • [Journal Article] エピジェネティクスで組織可塑性を理解する2012

    • Author(s)
      竹内純
    • Journal Title

      実験医学(羊土社)

      Volume: 30 Pages: 2896-2901

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 心臓発生と心疾患のエピジェネティクス -クロマチンモデリング因子・ヒストン修飾因子が織りなす複雑な臓器発生機構のモデルとして-2012

    • Author(s)
      中村遼、塚原由布子、竹内純
    • Journal Title

      実験医学(羊土社)

      Volume: 30 Pages: 2923-2931

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 心臓発生とその分子メカニズム2012

    • Author(s)
      森田唯加、小柴和子、竹内純
    • Journal Title

      血管医学(メディカルレビュー社)

      Volume: 13 Pages: 97-113

    • Related Report
      2012 Annual Research Report
  • [Journal Article] 心臓発生にかかわるクロマチン・ヒストン制御の役割2011

    • Author(s)
      塚原由布子、小柴和子、竹内純
    • Journal Title

      Heart View

      Volume: Vol. 15 No.8 Pages: 55-63

    • Related Report
      2012 Final Research Report
  • [Journal Article] Epigenetic factors and cardiac development2011

    • Author(s)
      van Weerd JH, Koshiba-Takeuchi K, Kwon C, Takeuchi JK.
    • Journal Title

      Cardiovascular Res.

      Volume: 91 Pages: 203-11

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Chromatin Remodeling Complex Dosage Modulates Transcription Factor Function in Heart Development2011

    • Author(s)
      Takeuchi JK, Lou X, Alexander JM, Sugizaki H, Delgado-Olguin P, Holloway AK, Mori A, Wylie JN, Munson C, Zhu Y, Yu-Qing Zhou9, Ru-Fang Yeh6, Henkelman RM, Harvey RP, Metzger D, Chambon P, Stainier DYR, Pollard KS, Scott IC, & Bruneau BG
    • Journal Title

      Nature Communications

      Volume: 1187 Pages: 1-11

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 心臓発生と心筋分化誘導のマスター因子2011

    • Author(s)
      竹内純 、宮川-富田幸子、笹岡陽介、 小柴和子
    • Journal Title

      Annual Review循環器

      Pages: 1-16

    • Related Report
      2012 Final Research Report
  • [Journal Article] Epigenetic factors and cardiac development2011

    • Author(s)
      Jan Hendrick van Weerd, Jun K.Takeuchil, et al.
    • Journal Title

      Cardiovasc.Res.

      Volume: 91 Pages: 203-211

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chromatin remodelling complex dosage modulates transcription factor function in heart development.2011

    • Author(s)
      Takeuchi JK, et al.
    • Journal Title

      Nature Communications

      Volume: 187(掲載確定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 心臓再生医療を目指した幹・前駆細胞からの利用状況と応用戦略2010

    • Author(s)
      杉崎弘江、 竹内純
    • Journal Title

      実験医学

      Volume: Vol.28 Pages: 62-69

    • Related Report
      2012 Final Research Report
  • [Presentation] 心臓構成細胞の運命決定と分化可塑性2012

    • Author(s)
      竹内純
    • Organizer
      次世代医学セミナー・ワークショップ
    • Place of Presentation
      福島県(招待講演)
    • Year and Date
      2012-02-28
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心筋細胞を創るプログラム因子と護るリモデリング因子2012

    • Author(s)
      竹内純
    • Organizer
      第6回フロンティアサイエンス機構サイエンスセミナー
    • Place of Presentation
      石川県(招待講演)
    • Year and Date
      2012-02-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心臓発生と心筋分化誘導のマスター因子2012

    • Author(s)
      竹内純
    • Organizer
      第41回日本心脈管作動物質学会
    • Place of Presentation
      秋田県(招待講演)
    • Year and Date
      2012-02-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新たな心臓前駆細胞制御因子と階層性の理解2012

    • Author(s)
      森田唯加、竹内純, 他
    • Organizer
      第41回日本心脈管作動物質学会
    • Place of Presentation
      秋田県(招待講演)
    • Year and Date
      2012-02-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Sall+ Cells Represent a Renewing cardiac Progenitor Population2012

    • Author(s)
      森田唯加、竹内純, 他
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Keystone, USA(招待講演)
    • Year and Date
      2012-01-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Chromatin Formation is Necessary for Cardiomyocyte Regeneration in Mammal/Amphibiam Models2012

    • Author(s)
      小柴和子、竹内純, 他
    • Organizer
      Keystone Symopsia on Molecular and Cellular Biology
    • Place of Presentation
      Keystone, USA(招待講演)
    • Year and Date
      2012-01-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] Rate-limiting Function of Chromatin/Histone Modulators for Cardiac Specification2011

    • Author(s)
      竹内純
    • Organizer
      The 28th Annual Meeting of the International Society for Heart Research Japanese Section
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-12-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心疾患発症とエピジェネティック因子群2011

    • Author(s)
      竹内純
    • Organizer
      大阪大学蛋白質研究所セミナー「疾患におけるエピゲノム異常の分子機構」
    • Place of Presentation
      大阪(招待講演)
    • Year and Date
      2011-11-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心臓を造る因子と護る因子2011

    • Author(s)
      竹内純
    • Organizer
      東京医科歯科大学難治疾患研究所「難治疾患共同研究拠点」事業による研究集会
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-10-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] マウスが紐解く心臓研究のアプローチ2011

    • Author(s)
      竹内純
    • Organizer
      日本遺伝学会第83回大会
    • Place of Presentation
      京都(招待講演)
    • Year and Date
      2011-09-22
    • Related Report
      2011 Annual Research Report
  • [Presentation] 胚性・体性心臓前駆細胞をマークする新規因子の特異な分化制御機構2011

    • Author(s)
      森田唯加、竹内純, 他
    • Organizer
      第2回Molecular Cardiovasucular Conference II
    • Place of Presentation
      北海道(招待講演)
    • Year and Date
      2011-09-03
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心臓誘導と心疾患:エピジェネティック因子群の機能解析からわかったこと2011

    • Author(s)
      竹内純
    • Organizer
      第5回神戸生活習慣病研究会
    • Place of Presentation
      兵庫県(招待講演)
    • Year and Date
      2011-07-23
    • Related Report
      2011 Annual Research Report
  • [Presentation] エピジェネティクスと心臓研究2011

    • Author(s)
      竹内純
    • Organizer
      第13回アテロジェネシス研究会
    • Place of Presentation
      岐阜県(招待講演)
    • Year and Date
      2011-07-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] Cell-Fate Speficiation of Cardiac Progenitor/Stem Cells by Defined Factors in vivo2011

    • Author(s)
      小柴和子、竹内純, 他
    • Organizer
      ISSCR 9th Annual Meeting
    • Place of Presentation
      Toronto, Canada(招待講演)
    • Year and Date
      2011-06-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] Chromatin Remodeling and Heart Cell-Fate Specification2011

    • Author(s)
      竹内純
    • Organizer
      162th IMEG Seminar
    • Place of Presentation
      熊本(招待講演)
    • Year and Date
      2011-04-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] 心疾患発症におけるエピジェネティクス因子群2011

    • Author(s)
      竹内純
    • Organizer
      日本医学総会
    • Place of Presentation
      東京(招待講演)
    • Year and Date
      2011-04-08
    • Related Report
      2011 Annual Research Report
  • [Presentation] Chromatin controls cardiac cell fates and keeping a healthy heart.2010

    • Author(s)
      竹内純
    • Organizer
      第33回 日本分子生物学会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2010-12-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] Direct differentiation to Cardiac cells by defined factors.2010

    • Author(s)
      竹内純
    • Organizer
      BIT's 2nd Annual International Congress of Cardiology
    • Place of Presentation
      上海コンベンションセンター(上海・中国)
    • Year and Date
      2010-12-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] Rate-limiting chromatin factors define the individual cardiac cell fate.2010

    • Author(s)
      竹内純
    • Organizer
      第14回 日本心不全学会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2010-10-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] 心臓発生を紐解くクロマチンモデリング因子研究2010

    • Author(s)
      竹内純
    • Organizer
      第1回 Molecular Cardiovascular Conference
    • Place of Presentation
      キロロ ホテルピアノ(北海道)
    • Year and Date
      2010-09-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] 心臓発生を紐解くクロマチンモデリング因子研究2010

    • Author(s)
      竹内純
    • Organizer
      第9回 心臓血管発生研究会
    • Place of Presentation
      シェラトン・グランテ"・トーキョーベイ(浦安)
    • Year and Date
      2010-07-10
    • Related Report
      2010 Annual Research Report
  • [Presentation] Epigenetic signal pathway controls cardiac hypertrophic signaling by modulating fetal gene programs.2010

    • Author(s)
      竹内純
    • Organizer
      第43回 発生生物学会
    • Place of Presentation
      国立京都国際会館(京都)
    • Year and Date
      2010-06-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Cardiac transcription factors2010

    • Author(s)
      竹内純
    • Organizer
      World Congress of Cardiology Scientific Sessions 2010
    • Place of Presentation
      中国国際会議場(北京・中国)
    • Year and Date
      2010-06-19
    • Related Report
      2010 Annual Research Report
  • [Presentation] The novel mechanism of histonechromatin regulation for cardiomyocytes regeneration

    • Author(s)
      Ryo Nakamura, Kazuko Koshiba-Takeuchi, Jun K Takeuchi, et al.
    • Organizer
      2012 Weinstein cardiovascular development conference
    • Place of Presentation
      Chicago USA
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Sall+ Cells Represent a Renewing cardiac Progenitor Population

    • Author(s)
      Yuika Morita, Yuko Tsukahara, Jun K Takeuchi, et al.
    • Organizer
      2012 Weinstein cardiovascular development conference
    • Place of Presentation
      Chicago USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Cell-Fate Speficiation of Cardiac Progenitors/Stem Cells by Defined Factors in vivo and in vitro

    • Author(s)
      Yuika Morita, Yuko Tsukahara, Peter Andersen, Jun K Takeuchi, et al.
    • Organizer
      第45回日本発生生物学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] Epigenetic factors and the capacity for heart regeneration in mammals

    • Author(s)
      Ryo Nakamura, Kazuko Koshiba-Takeuchi, Jun K Takeuchi, et al.
    • Organizer
      第45回日本発生生物学会
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Presentation] クロマチン因子から見る心臓再生と心筋可塑性

    • Author(s)
      竹内純
    • Organizer
      第55回日本腎臓学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 心臓再生向上因子としてのクロマチン制御機構

    • Author(s)
      中村遼、小柴和子、塚原由布子、竹内純
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Sallは心臓前駆細胞必須因子として全心臓細胞系譜を制御する

    • Author(s)
      森田唯加、塚原由布子、小柴和子、竹内純
    • Organizer
      第11回日本再生医療学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Sall promotes cardiac progenitor cell fate and fully contribute to cardiomyocyte lineages

    • Author(s)
      Yuika Morita, Yuko Tsukahara, Jun K Takeuchi, et al.
    • Organizer
      第10回国際幹細胞学会(ISSCR)年次総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] Fetal epigenetic modifiers stimulate cardiomyocyte regeneration and protect fibrosis in mammalian/ampfibian models

    • Author(s)
      Kazuko Koshiba-Takeuchi, Ryo Nakamura, Jun K Takeuchi, et al.
    • Organizer
      第10回国際幹細胞学会(ISSCR)年次総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] 心臓再生能力を司るクロマチン結合制御因子群

    • Author(s)
      竹内純
    • Organizer
      33回日本炎症・再生医学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] 特定転写因子による心臓幹・前駆細胞運命プログラム機構

    • Author(s)
      森田唯加、塚原由布子、竹内純、他
    • Organizer
      第3回Molecular Cardiovascular ConferenceII
    • Place of Presentation
      北海道
    • Related Report
      2012 Annual Research Report
  • [Presentation] 心筋再生におけるエピゲノム制御機構

    • Author(s)
      中村遼、小柴和子、塚原由布子、竹内純、他
    • Organizer
      第11回日本心臓血管発生研究会
    • Place of Presentation
      福島
    • Related Report
      2012 Annual Research Report
  • [Presentation] 特定転写因子による心臓幹・前駆細胞運命プログラム機構

    • Author(s)
      森田唯加、塚原由布子、竹内純、他
    • Organizer
      第11回日本心臓血管発生研究会
    • Place of Presentation
      福島
    • Related Report
      2012 Annual Research Report
  • [Presentation] Sa+ Cells, a Novel Cardiac Lineage, Promote Heart Program and Its Regeneration

    • Author(s)
      Yuika Morita, Jun K. Takeuchi
    • Organizer
      第29回国際心臓研究学会(ISHR)日本部会総会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 新規心臓転写因子による心臓細胞運命決定と機能的な心臓再生

    • Author(s)
      森田唯加、塚原由布子、竹内純、他
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 心臓再生における統合的なクロマチン構造変換

    • Author(s)
      中村遼、小柴和子、塚原由布子、竹内純、他
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dnmt1 specifically functions in heart development and maintenance

    • Author(s)
      山田小和加、竹内純、他
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] 心疾患重篤化と心機能再生に関わるエピジェネティック因子群

    • Author(s)
      竹内純
    • Organizer
      奈良県立医科大学セミナー
    • Place of Presentation
      奈良
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Epigenetic Factors in Cardiac Development and Regeneration

    • Author(s)
      竹内純
    • Organizer
      第7回日仏先端科学(JFFoS)シンポジウム
    • Place of Presentation
      滋賀
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] How to Build a Four Chambered Heart: Molecular Mechanism Underlying Atrial and Ventricular Septation in Vertebrate Heart

    • Author(s)
      Yuuta Moriyama, Shoji Kawakami, Jun K Takeuchi, et al.
    • Organizer
      CDBシンポジウム「The Making of a Vertebrate.」
    • Place of Presentation
      神戸
    • Related Report
      2012 Annual Research Report
  • [Book] Heart View2011

    • Author(s)
      塚原由布子、竹内純, 他
    • Publisher
      メジカルビュー社
    • Related Report
      2011 Annual Research Report
  • [Book] 循環器2011

    • Author(s)
      竹内純, 他
    • Publisher
      中外医学社
    • Related Report
      2010 Annual Research Report
  • [Book] 実験医学2010

    • Author(s)
      杉崎弘江、竹内純
    • Publisher
      羊土社
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.iam.u-tokyo.ac.jp/junktakeuchi-lab/index.html

    • Related Report
      2012 Final Research Report
  • [Remarks] 東京大学分子細胞生物学研究所 心循環器再生研究分野 竹内純研究室

    • URL

      http://www.iam.u-tokyo.ac.jp/junktakeuchi-lab/index.html

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://www.iam.u-tokyo.ac.jp/junktakeuchi-lab/index.html

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.iam.u-tokyo.ac.jp/NatureCommunication_20100208.html

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 特定因子による心臓幹・前駆細胞の誘導/活性化方法2012

    • Inventor(s)
      竹内純、森田唯加、塚原由布子
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-12-21
    • Related Report
      2012 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 高効率心臓細胞分化能を持った新規心臓前駆(幹)細胞制御因子の樹立法2012

    • Inventor(s)
      竹内純, 他
    • Industrial Property Rights Holder
      竹内純, 他
    • Industrial Property Number
      2012-011458
    • Filing Date
      2012-01-23
    • Related Report
      2011 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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