biostudies-literatureUnknownAmrute JMNHLBI NIH HHSNCI NIH HHSNIAMS NIH HHSInflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk in human cardiac disease remains unexplored and there are currently no therapeutics to target fibrosis. Here, we performed multi-omic single-cell gene expression, epitope mapping, and chromatin accessibility profiling in 38 donors, acutely infarcted, and chronically failing human hearts. We identified a disease-associated fibroblast trajectory marked by cell surface expression of fibroblast activator protein (FAP), which diverged into distinct myofibroblasts and pro-fibrotic fibroblast populations, the latter resembling matrifibrocytes. Pro-fibrotic fibroblasts were transcriptionally similar to cancer associated fibroblasts and expresResearch squarers.3.rs-2402606https://www.ebi.ac.uk/biostudies/studies/S-EPMC9900986biostudies-literatureTargeting Immune-Fibroblast Crosstalk in Myocardial Infarction and Cardiac Fibrosis.PMC9900986P30 CA091842P30 AR073752R01 HL138466R35 HL161185R01 HL151078R01 HL139714Ma PLee PHeo GSKuppe CLavine KJJones CBredemeyer AKoenig ALLiu YLi CMKadyrov FFurtado MKramann RAmrute JMAson BKreisel DPenna VTerada YFu AStitziel NOYamawaki TLuo XHayat SYang SKopecky BShi SYfalseTargeting Immune-Fibroblast Crosstalk in Myocardial Infarction and Cardiac Fibrosis.Inflammation and tissue fibrosis co-exist and are causally linked to organ dysfunction. However, the molecular mechanisms driving immune-fibroblast crosstalk in human cardiac disease remains unexplored and there are currently no therapeutics to target fibrosis. Here, we performed multi-omic single-cell gene expression, epitope mapping, and chromatin accessibility profiling in 38 donors, acutely infarcted, and chronically failing human hearts. We identified a disease-associated fibroblast trajectory marked by cell surface expression of fibroblast activator protein (FAP), which diverged into distinct myofibroblasts and pro-fibrotic fibroblast populations, the latter resembling matrifibrocytes. Pro-fibrotic fibroblasts were transcriptionally similar to cancer associated fibroblasts and expres2023-01-01T00:00:00Z2023 Jan2026-06-25T03:13:55.865Z2026-06-25T03:07:51.782ZS-EPMC99009863674787810.21203/rs.3.rs-2402606/v1