GSE132144
Single cell RNA-seq analysis reveals the crucial role of Collagen triple helix repeat containing 1 (Cthrc1) cardiac fibroblasts for ventricular remodeling after myocardial infarction [scRNA-seq]
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, express high levels of the hormone CTHRC1 and of the immunomodulatory co-receptor CD200, and localize to the wounded myocardium. Combining epigenomic profiling with functional assays, we unveil important candidate regulators mediating their response to cardiac damage. We show that the absence of CTHRC1, a top marker of this activated fibroblast subpopulation, results in pronounced lethality due to ventricular rupture within the first week post-myocardial infarction. Finally, we find evidence for the existence of similar mechanisms in a pig pre-clinical model of MI and establish a positive correlation between Cthrc1 levels and cardiac function after MI. Overall design: Time-course study of cardiac fibroblasts after myocardial infarction. Samples include Healthy Myocardium (Control) and 7, 14 and 30 days post-infarction. Cardiac fibroblasts were also selected (mEFSK4) from Cthrc1-KO mice 7 days post-infarction.