Single-cell and bulk RNA sequencing of mouse atherosclerosis disease stage course [aorta_scRNA-Seq]

Atherosclerotic coronary artery disease (CAD) development encompasses endothelial dysfunction, vascular infiltration of immune cells and smooth muscle cell dedifferentiation. However, the specific disease-associated transcriptional changes occurring within each of the major lesional cell types remain incompletely characterized. Here, we identify disease-associated cell states within the major aortic cell types and investigate the similarities and differences in their gene signatures compared to each other and to healthy (non-diseased) cells. By integrating human genetic association data and generating polygenic risk scores, we further use the atherosclerosis-associated cell state gene signatures to interrogate how the perturbed states of different lesional cell types contribute to the genetic risk for CAD. Overall design: A disease stage course of atherosclerosis in mouse was established by varying genotype (wild type and proatherogenic) and diet (0, 1 or 3 months of high-fat diet), followed by scRNA-Seq (all cell types) and bulk RNA-Seq of the thoracic aorta.