Meta-analysis of smooth muscle lineage transcriptomes in atherosclerosis and their relationships to in vitro models

We identified 24 cell clusters in the meta-analysis of single cells from atheroscleroticlesions with notable heterogeneity across studies, especially for macrophage populations. Trajectory analysis of VSMC lineage positive cells revealed several possible paths of state transitions with one traversing from contractile VSMC to macrophages by way of a proliferative cell cluster. Transcriptome comparisons between in vivo and in vitro states underscored that data from three (in vitro) cholesterol treated VSMC experiments did not mirror cell state transitions observed in vivo. However, all in vitro macrophage profiles analyzed (M1, M2, and oxLDL) were more similar to in vivo profiles of macrophages than VSMC were to in vivo profiles of VSMCs, with oxLDL loaded macrophages showing the most similarity to in vivo states. Overall design: Meta-analysis of scRNA-seq data from VSMC lineage traced cells across five experiments of murine atherosclerosis was performed. In vivo expression profiles were compared to three in vitro datasets of VSMCs loaded with cholesterol and three datasets of polarized macrophages.