Endothelial reprogramming by disturbed flow revealed by single-cell RNAseq and chromatin accessibility study

Disturbed flow (d-flow) induces atherosclerosis by regulating gene expression in endothelial cells (ECs). For further mechanistic understanding, we carried out a single-cell RNA sequencing (scRNAseq) and scATACseq study using endothelial-enriched single-cells from the left- and right carotid artery exposed to d-flow (LCA) and stable-flow (s-flow in RCA) using the mouse partial carotid ligation model. We found 8 EC clusters along with immune cells, fibroblasts, and smooth muscle cells. Analyses of marker genes, pathway and pseudo-time revealed that ECs are highly heterogeneous and plastic. D-flow induced a dramatic transition of ECs from atheroprotective phenotypes to pro-inflammatory, mesenchymal (EndMT), hematopoietic stem cells, endothelial stem cells and progenitor cells, and endothelial-immune cell-like transition.