2020/03/01 by Elvira Forte, Daniel A. Skelly, Mandy Chen +7 · 1 voice · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Cardiac Fibrosis and Remodeling #Cardiovascular Function and Risk Factors #Signaling Pathways in Disease
paper · pdf · doi:10.1016/j.celrep.2020.02.008
openalex publication_date 2020/03/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Cardiac ischemia leads to the loss of myocardial tissue and the activation of a repair process that culminates in the formation of a scar whose structural characteristics dictate propensity to favorable healing or detrimental cardiac wall rupture. To elucidate the cellular processes underlying scar formation, here we perform unbiased single-cell mRNA sequencing of interstitial cells isolated from infarcted mouse hearts carrying a genetic tracer that labels epicardial-derived cells. Sixteen interstitial cell clusters are revealed, five of which were of epicardial origin. Focusing on stromal cells, we define 11 sub-clusters, including diverse cell states of epicardial- and endocardial-derived fibroblasts. Comparing transcript profiles from post-infarction hearts in C57BL/6J and 129S1/SvImJ inbred mice, which displays a marked divergence in the frequency of cardiac rupture, uncovers an early increase in activated myofibroblasts, enhanced collagen deposition, and persistent acute phase response in 129S1/SvImJ mouse hearts, defining a crucial time window of pathological remodeling that predicts disease outcome.