Single-cell omics analysis to develop the therapy for heart failure via cardiomyocyte reprogramming

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03649
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• 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): 2019-04-01 – 2022-03-31
• Keywords: 心不全 / シングルセル解析 / 心筋リプログラミング

Outline of Final Research Achievements

By using single-cell RNA-seq analysis, we clarified that cardiomyocytes diverge into adaptive and failing cardiomyocytes in the onset of heart failure, and DNA damage and activation of p53 signaling are important in the induction of failing cardiomyocytes. Next, by extracting cell-cell interactions from single-cell data, we revealed that the interplay of TGF-beta signaling between cardiac fibroblasts and cardiomyocytes induces cardiomyocyte senescence. By integrating spatial transcriptome and single-cell RNA-seq of the post-myocardial infarction heart, we identified mechanosensing gene-positive cardiomyocytes that appear at the border zone of myocardial infarction, and revealed that they adaptively regulate the formation of cardiac remodeling.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

心不全は、心臓のポンプ機能の低下によって全身に十分な量の血液を送れなくなる病態であり、がんと並んで世界中で多くの患者の命を脅かしています。これまで心不全がなぜ起こるのかわからない点が多かったのですが、我々は心臓を構成する細胞を取り出してそれぞれの細胞に含まれる全ての遺伝子を読み取る技術を確立してその疑問を明らかにすることができました。今後は、この研究で明らかになった心不全のメカニズムに基づいた新しい治療法を開発していきます。