Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury

Besides cardiomyocytes (CM), the heart contains numerous stromal cell types which play key roles in heart repair, regeneration and disease, including fibroblast, vascular and immune cells. However, a comprehensive understanding of this interactive cell community is lacking. We performed single cell RNA-sequencing of the total non-CM fraction and enriched (Pdgfra-GFP+) fibroblast lineage cells from murine hearts at days 3 and 7 post-sham or myocardial infarction surgery. Clustering of >30,000 single cells allowed us to identify >30 populations representing 9 cell lineages, included a previously undescribed fibroblast lineage trajectory present in both sham and MI hearts leading to a uniquely activated cell state defined in part by a strong anti-WNT transcriptome signature. We also defined three novel myofibroblast subtypes expressing either pro-fibrotic or anti-fibrotic signatures, and 8 macrophage subsets. These comprehensive cardiac single cell transcriptome data provide an entry point for deeper analysis of cardiac homeostasis, inflammation, fibrosis, repair and regeneration.