Cardiomyocyte herogeneity in heart failure

• Project/Area Number: 15K19371
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Nomura Seitaro 東京大学, 医学部附属病院, 特任助教 (10722118)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 分子心臓学 / ゲノム科学 / 分子心臓病学 / 循環器内科学 / 循環器 / １細胞解析 / 遺伝子発現

Outline of Final Research Achievements

This study has aimed to assess the cardiomyocyte heterogeneity during heart failure and uncover the significance of this heterogeneity for the development of heart failure. Having analyzed single-cardiomyocyte transcriptomes, we revealed the transcriptional heterogeneity in cardiomyocytes during heart failure. RNA in situ hybridization analysis showed the spatial heterogeneity in expression of genes characteristic for heart failure progression. We also identified the factors that are heterogeneously expressed as the cause of heart failure progression. This study not only establishes the method to analyze the cellular heterogeneity, but also demonstrates its usefulness in dissecting disease pathogenesis.

Research Products

• [Journal Article] Negative feedback loop of bone resorption by NFATc1-dependent induction of Cadm1. (2017)
  • Author(s): Nakamura S, Koyama T, Izawa N, Nomura S, Fujita T, Omata Y, Minami T, Matsumoto M, Nakamura M, Fujita-Jimbo E, Momoi T, Miyamoto T, Aburatani H, Tanaka S.
  • Journal Title: PLoS One Volume: 12 Issue: 4 Pages: e0175632-e0175632
  • DOI: 10.1371/journal.pone.0175632
  • Peer Reviewed / Open Access
• [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 Issue: 3 Pages: 0174099-0174099
  • DOI: 10.1371/journal.pone.0174099
  • Peer Reviewed / Open Access
• [Journal Article] CellTree: an R/bioconductor package to infer the hierarchical structure of cell populations from single-cell RNA-seq data (2017)
  • Author(s): duVerle DA, Yotsukura S, Nomura S, Aburatani H, Tsuda K
  • Journal Title: BMC Bioinformatics Volume: 17 Issue: 1 Pages: 363-363
  • DOI: 10.1186/s12859-016-1175-6
  • Peer Reviewed / Open Access
• [Journal Article] Hypoxia-Inducible Factor-1α Activates the Transforming Growth Factor-β/SMAD3 Pathway in Kidney Tubular Epithelial Cells. (2016)
  • Author(s): Kushida N, Nomura S, Mimura I, Fujita T, Yamamoto S, Nangaku M, Aburatani H.
  • Journal Title: American Journal of Nephrology Volume: 44 Pages: 276-285
  • Peer Reviewed
• [Journal Article] Activation of endothelial β-catenin signaling induces heart failure. (2016)
  • Author(s): Nakagawa A, Naito AT, Sumida T, Nomura S, Shibamoto M, Higo T, Okada K, Sakai T, Hashimoto A, Kuramoto Y, Oka T, Lee JK, Harada M, Ueda K, Shiojima I, Limbourg FP, Adams RH, Noda T, Sakata Y, Akazawa H, Komuro I.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 25009-25009
  • DOI: 10.1038/srep25009
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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 Issue: 4 Pages: 799-808
  • DOI: 10.1161/circheartfailure.114.001958
  • 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 receptors (2015)
  • 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 Issue: 6 Pages: e0127445-e0127445
  • DOI: 10.1371/journal.pone.0127445
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Quantitative measurement of GPCR endocytosis via pulse-chase covalent labeling (2015)
  • 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 Issue: 5 Pages: e0129394-e0129394
  • DOI: 10.1371/journal.pone.0129394
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Genetics of Cardiomyopathy (2017)
  • 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: 2017-03-19
  • 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
  • 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