Diversity of arterial cell and phenotypic heterogeneity induced by high-fat and high-cholesterol diet

Objective: Disturbed blood flow characterized by low and oscillatory shear stress and complex microenvironment is one of the causes of the atherosclerosis progression. During the development, endothelial cells generally develop into a dysfunction state, so do other cells. To further analyze the heterogeneity of different cell types, single-cell RNA sequencing was used to provide detailed transcriptomic information.Approach and results: Transcriptional analysis of single cells from aortic arch of 16-week Apoe-/- mice under normal and atherosclerotic condition was carried out using single-cell RNA sequencing. By unsupervised clustering, 10 types of cells were identified: endothelial cells, immune cells, fibroblasts, erythroids, smooth muscle cells, cycling basal cells, clara cells, mesothelial cells, adipocytes and neurons. Among these cells, endothelial cells and immune cells exhibited great heterogeneity especially between normal and atherosclerotic group. Gene expression profile of later screened cells identified ten subpopulations of endothelial cells of different functions. Distribution of these cells in the control group and HFD group varies. Immune cells consist of macrophages, foam cells, B cells, T cells, neutrophils and NK cells mainly. During the data processing, the cell sorting is done by recognition with specific markers and rules.Conclusions: Our data provide a comprehensive description of all kinds of cells in aortic arch and the heterogeneity brought by western diet. These findings open a new sight into the transcriptional development of atherosclerosis.