Single-cell transcriptome analysis reveals cellular heterogeneity in the ascending aortas of normal and high-fat diet-fed mice

The aorta contains numerous cell types that contribute to vascular inflammation and thus the progression of aortic diseases. However, the heterogeneity and cellular composition of the ascending aorta in the setting of a high-fat diet (HFD) have not been fully assessed. We performed single-cell RNA sequencing on ascending aortas from mice fed a normal diet and mice fed a HFD. Unsupervised cluster analysis of the transcriptional profiles from 24,001 aortic cells identified 27 clusters representing 10 cell types: endothelial cells (ECs), fibroblasts, vascular smooth muscle cells (SMCs), immune cells (B cells, T cells, macrophages, and dendritic cells), mesothelial cells, pericytes, and neural cells. After HFD intake, subpopulations of endothelial cells with lipid transport and angiogenesis capacity and extensive expression of contractile genes were defined. In the HFD group, three major SMC subpopulations showed increased expression of extracellular matrix-degradation genes, and a synthetic SMC subcluster was proportionally increased. This increase was accompanied by upregulation of proinflammatory genes. Under HFD conditions, aortic-resident macrophage numbers were increased, and blood-derived macrophages showed the strongest expression of proinflammatory cytokines. Our study elucidates the nature and range of the cellular composition of the ascending aorta and increases understanding of the development and progression of aortic inflammatory disease. Cardiovascular disease: High-fat diets cause changes to aorta cells RNA sequencing of aorta cells reveals how key changes in cell populations and gene expression caused by a high-fat diet can increase risk of cardiovascular diseases. Xin Ma and co-workers at Jiangnan University in Wuxi, China, performed single-cell sequencing on over 24,000 cells from the ascending aorta of mice fed either high-fat or normal diets. The resulting dataset of around 1,700 genes and 4,000 unique molecular identifiers reveals numerous fat-induced differences across the ten main aortic cell types. The high-fat diet extended specific sub-populations of endothelial cells that enhance lipid transport, while muscle cells showed increased expression of genes that degrade the extracellular matrix. Other fat-induced differences, including increased populations of immune cells known as macrophages and a sub-cluster of muscle cells that up-regulate pro-inflammatory genes, may act to promote excessive immune responses in obese individuals.