Molecular discovery research targeting cardiac remodeling using multi-directional transcriptional profiling and therapeutic application

• Project/Area Number: 26860558
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: Higo Shuichiro 大阪大学, 医学(系)研究科(研究院), 助教 (00604034)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 心不全 / 心臓リモデリング / 高速シークエンサー / トランスオミクス / 線維芽細胞

Outline of Final Research Achievements

For exploratory research aimed at regulatory mechanisms underlying pathological proliferation of non-cardiomyocytes during the progression of cardiac remodeling, we applied H3K4me3 mapping and RNA-sequence to pressure-overloaded hearts of mice. From the combination of Epigenomics and Transcriptomics, we identified a set of genes involved in interstitial fibrosis, and identidied a transcription factor specifically expressed in interstitial cardiac fibroblasts. The transcription factor is expressed in a limited population of fbroblasts and required for reactive proliferation. Next, to clarify unknown regulating mechanisms underlying hypertrophic response in cardiomyocytes, we combined quantitative RNA imaging and ChIP-sequence and identified a negative regulator of cardiomyocyte hypertropy. Our exploratory analysis identifies pathologically relevant molecules using a combination of multidimensional datasets and suggests the usefulness of TransOmics in cardiovascular pathophysiology.

Research Products

• [Journal Article] Higdla is a oositive regulaator of cytochrome c oxidase (2015)
  • 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. Nat. Acad. Sci. U.S.A. Volume: 112 Issue: 5 Pages: 1553-1558
  • DOI: 10.1073/pnas.1419767112
  • Peer Reviewed / Open Access
• [Journal Article] Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5. (2015)
  • Author(s): Yan Y, Tsukamoto O, Nakano A, Kato H, Kioka H, Ito N, Higo S, Yamazaki S, Shintani Y, Matsuoka K, Liao Y, Asanuma H, Asakura M, Takafuji K, Minamino T, Asano Y, Kitakaze M, Takashima S.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 6137-6137
  • DOI: 10.1038/ncomms7137
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Single Cell Imaging Analysis Clarifies RNA Quantity Control Mechanism in Cardiomyocytes (2016)
  • Author(s): Yuki Masumura, Shuichiro Higo、Yoshihiro Asano、Hisakazu Kato、Yi Yan、Osamu Tsukamoto、Hidetaka Kioka、Takaharu Hayashi、Yasunori Shintani、Satoru Yamazaki、Tetsuo Minamino、Masafumi Kitakaze、Issei Komuro、Seiji Takashima、Yasushi Sakata.
  • Organizer: 第80回日本循環器学会学術集会 Young Investigator's Award Finalists Lectures (Basic Research)
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2016-03-18
• [Presentation] Molecular Discovery Research using TransOmics in Cardiovascular Pathophysiology. (2015)
  • Author(s): Shuichiro Higo, Yuki Masumura, Yoshihiro Asano, Issei Komuro, Masafumi Kitakaze, Yasushi Sakata and Seiji Takashima.
  • Organizer: 第79回日本循環器学会学術集会 シンポジウム
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2015-04-24
• [Presentation] Meox1 is a Cell-cycle Oscillator Required for Mitotic Transition and Proliferation in Cardiac Fibroblasts (2014)
  • Author(s): Shuichiro Higo, Yoshihiro Asano, Yuki Masumura, Yasushi Sakata, Masafumi Kitakaze, Seiji Takashima
  • Organizer: BASIC CARDIOVASCULAR SCIENCES 2014 SCIENTIFIC SESSIONS
  • Place of Presentation: Las Vegas, Nevada, USA
  • Year and Date: 2014-07-14 – 2014-07-17
• [Presentation] 定量的エピゲノム解析を用いた心臓線維芽細胞における細胞周期制御因子の同定 (2014)
  • Author(s): 肥後 修一朗、朝野 仁裕、増村 雄喜、坂田 泰史、澤 芳樹、北風 政史、小室 一成、高島 成二
  • Organizer: 第51回日本臨床分子医学会
  • Place of Presentation: 東京
  • Year and Date: 2014-04-11