Decoding the transcriptome of calcified atherosclerotic plaque at single-cell resolution

Atherogenesis involves an interplay of inflammation, tissue remodeling and cellular transdifferentiation (CTD), making it especially difficult to precisely delineate its pathophysiology. Here we examine the single-cell transcriptome of entire calcified atherosclerotic core (AC) plaques and patient-matched proximal adjacent (PA) portions of carotid artery tissue from patients undergoing carotid endarterectomy. We use a novel tissue dissociation strategy, single-cell RNA sequencing, and systems-biology approaches to analyze the transcriptional profiles of six main cell populations and identify key gene drivers of pathogenic biological processes in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). Calcified atherosclerotic core (AC) plaques and patient-matched proximal adjacent (PA) portions of carotid artery were collected from three patients undergoing carotid endarterectomy and were assessed using single cell RNA-seq