Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques by [email protected]; [email protected] ISBN 101038/S4416102500628Y instant download

Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques by [email protected]; [email protected] ISBN 101038/S4416102500628Y instant download

Carotid stenosis causes ischemic stroke in both sexes, but the clinical presentation and plaque characteristics difer. Here we run deep single-cell Check for updatessequencing of 7,690 human carotid plaque cells from male and female patients. While we found no sex diferences in major cell types, we identifed a predominance of the osteogenic phenotype in smooth muscle cells, immunomodulating macrophages (MPs) and endothelial cells (ECs) undergoing endothelial-to-mesenchymal transition in females. In males, we found smooth muscle cells with the chondrocytic phenotype, MPs involved in tissue remodeling and ECs with angiogenic activity. Sex-biased subcellular clusters were integrated with tissue-specifc gene-regulatory networks (GRNs) from the Stockholm–Tartu Atherosclerosis Reverse Network Engineering Task study. We identifed GRN195 involved in angiogenesis and T cell-mediated cytotoxicity in male ECs, while in females, we found GRN33 and GRN122 related to TREM2−/TREM1+ MPs and endothelial-to-mesenchymal transition. The impact of GRN195 on EC proliferation in males was functionally validated, providing evidence for potential therapy targets for atherosclerosis that are sex specifc.