Single-cell pathological dynamics in tissue repair and remodeling after myocardial infarction

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17587
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Ko Toshiyuki 東京大学, 医学部附属病院, 特任助教 (00836059)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 心不全 / 心筋梗塞 / シングルセル解析 / 空間的遺伝子発現解析

Outline of Final Research Achievements

This study aimed to perform spatiotemporal transcriptome analysis to understand the pathophysiology of myocardial infarction. To investigate the spatiotemporal regulation of gene expression in the heart after myocardial infarction, we performed single-nucleus RNA-seq and spatial transcriptome analysis on heart tissue on days 1, 7, and 14 after myocardial infarction or sham surgery. These analyses revealed that the expression of mechano-stress-responsive genes were up-regulated specifically in the ischemic border zone during the acute phase of post-infarction period. In addition, we found that Htra3, a gene identified by single-cell RNA-seq analysis of cardiac fibroblasts, plays a cardioprotective role in both pressure overload and ischemia.

Free Research Field

心不全

Academic Significance and Societal Importance of the Research Achievements

本研究で認められたメカノストレス関連遺伝子やHtra3はいずれも心筋梗塞においては心保護的な役割を果たしており、新規治療ターゲットであると言える。また、本研究で取得したシングルセル・シングル核RNA-seqやSpatial transcriptomeのデータが今後論文として公開されれば、今後他の研究にもpublic dataとして利用されることで、一層この分野の研究進展に資するものであると思われる。