Single-Cell Transcriptomics Analysis of Collagen1a2+ Lineages Reveals Endothelial Features of Cardiac Fibroblast

Understanding the nomenclature, defining markers, origins, heterogeneity, and plasticity of cardiac fibroblasts is of fundamental importance for cardiac fibroblast-targeted strategies. Here, by performing single-cell RNA-sequencing on Collagen1a2+ cardiac fibroblasts lineages post sham and cardiac hypertrophy, we deciphered how the preexisting cardiac fibroblasts respond to cardiac hypertrophy. Our study showed cells marked with Ifitm1 as the main origin of activated cardiac fibroblasts in response to cardiac hypertrophy; Based on the elaboration of endothelial features, two cell subpopulations are expected to be the target for cardiac repair as being found potential in blood vessel formation. Furthermore, we analyzed the relationship among the known cardiac fibroblast marker genes. Venn diagram analysis revealed five marker genes for high labeling of cardiac fibroblasts, which is suggested as Gsn>Dcn>Vim>Col1a2>Tcf21. Our work provides insights into the heterogeneity of cardiac fibroblasts with a new perspective, which is the foundation for accurate regulation of cardiac fibroblasts during the cardiac repair.