Single-Cell Transcriptomics Analysis of Cardiac Fibroblasts from the Collagen1a2 Lineage Reveals that They Show Endothelial Features

Cardiac fibroblasts (CFs) are a distinct cell type of mesenchymal origin with highly heterogeneous. A subset of CFs undergoing mesenchymal-endothelial transition (MEndoT) and contributes to cardiac repair by revascularizing the damaged myocardium. We used Col1a2CreERT:R26RtdTomato transgenic mice for tracking resident CFs (RCFs) and 10x scRNA-Seq analysis to determine the subgroup of pre-existing CFs involved in MEndoT that respond to transverse aortic constriction (TAC) injury. The cell trajectory assay showed the presence of cluster 1 RCFs showed the phenotype of stem cells, indicates that these clusters are diverse with regard to differentiation and directly contribute to angiogenesis. Sorted CD200+ CFs showed markedly higher expression levels of pro-angiogenesis-related genes and tube formation ability. Our findings indicated that CD200+ cells are the main group of CFs involved in MEndoT and plays a major role in cell differentiation. Our study will aid the development of new CF-targeted therapeutic strategies for treating cardiac hypertrophy.