Single-cell genomics reveals a novel cell state during smooth muscle cell phenotypic switching and potential therapeutic targets for atherosclerosis in mouse and human [human]

Smooth muscle cells (SMC) play significant roles in atherosclerosis via phenotypic switching, a pathological process in which SMC dedifferentiation, migration and transdifferentiation into other cell types. Yet, how SMC contribute to pathophysiology of atherosclerosis remains elusive. To reveal the trajectories of SMC transdifferentiation during atherosclerosis and to identify molecular targets for disease therapy, we combined SMC fate mapping and single-cell RNA sequencing of both mouse and human atherosclerotic plaques. Human atherosclerotic carotid arteries were obtained from three patients undergoing endarterectomy as part of a clinical research protocol approved by the Institutional Review Board (IRB) of Columbia University Irving Medical Center. All patients were fully informed of the research and signed IRB-approved informed consent forms. Single cells were digested from human atherosclerotic carotid arteries and the live cells were sorted for scRNA-seq using Chromium Single Cell Gene Expression system (10x Genomics).