{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:57:55Z","timestamp":1787763475315,"version":"build-2784847793"},"reference-count":39,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T00:00:00Z","timestamp":1748908800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470304"],"award-info":[{"award-number":["82470304"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>A comprehensive understanding of the genome-wide regulatory landscape of the cardiac tissues post-myocardial infarction (MI) is still lacking. We therefore integrated single-cell RNA sequencing (scRNA-seq) and single-cell for transposase-accessible chromatin sequencing (scATAC-seq) to elucidate the epigenetic landscape of the heart post-MI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We established MI mice through ligation of the left anterior descending coronary artery, and obtained cardiac tissues from mice at 1-, 3-, 7-, and 14-days post-MI. Integrative analyses of the scRNA-seq and scATAC-seq data revealed the presence of two novel fibroblast subpopulations in the cardiac tissues of MI mice, termed GATA-binding protein 5\/ISL LIM Homeobox 1 (GATA5\/ISL1)+ fibroblasts and GLI family zinc finger 3 (Gli3)high fibroblasts. The GATA5\/ISL1+ fibroblasts were characterized by fibroblast and cardiomyocyte signatures and were found to play a crucial role in cardiac repair post-MI. Moreover, adenoviral-mediated overexpression of GATA5 and ISL1 ameliorated cardiac function and attenuated myocardial fibrosis in the MI mice. RNA sequencing confirmed that GATA5 and ISL1 co-regulate Wnt signalling pathway to promote the transformation of fibroblasts into functional cardiomyocytes. Furthermore, analysis of the human cardiac tissues of MI patients also revealed the presence of GATA5\/ISL1+ fibroblasts in the scar tissues, suggesting their crucial role in cardiac tissue repair post-MI. In addition, proteomic analyses revealed enhanced cardiac repair and development signalling in the GATA5\/ISL1-overexpressing human cardiac fibroblasts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The study provides novel perspectives on the mechanisms of myocardial injury and repair at the single-cell level and indicates the potential role of GATA5 and ISL1 as therapeutic targets for MI treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf101","type":"journal-article","created":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T19:28:27Z","timestamp":1748978907000},"source":"Crossref","is-referenced-by-count":5,"title":["Single-cell epigenomic and transcriptomic analysis unveils the pivotal role of GATA5\/ISL1+ fibroblasts in cardiac repair post-myocardial infarction"],"prefix":"10.1093","author":[{"given":"Shuchen","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University , No. 121 Jiangjiayuan, Nanjing 210011 ,","place":["P. 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China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Wang","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, The Second Affiliated Hospital of Soochow University , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Chen","sequence":"additional","affiliation":[{"name":"Central Laboratory, The Second Affiliated Hospital of Soochow University , Suzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8290-9266","authenticated-orcid":false,"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Nanjing Medical University , No. 121 Jiangjiayuan, Nanjing 210011 ,","place":["P. R. 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