Unravelling the molecular activation of the reparative cardiac fibroblasts after myocardial infarction

Cardiac fibroblasts have a central role during the ventricular remodeling process associated to different types of cardiac injury. Recent studies have shown that fibroblasts do not respond homogeneously to heart damage, suggesting that the adult myocardium may contain specialized fibroblast subgroups with specific functions. Due to the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population dynamics in response to cardiac damage is still missing. Using single-cell RNA-seq we have identified and characterized a fibroblast subpopulation that emerges in response to myocardial infarction (MI) in a murine model. These activated fibroblasts exhibit a clear pro-fibrotic signature, and localize to the wounded myocardium. Combining epigenomic profiling with functional assays, we unveil important candidate regulators mediating their response to cardiac damage. Overall design: Time-course of study of cardiac fibroblasts after myocardial infarction. Samples include control, 3 and 5 days after myocardial infarction.