Single Cell Sequencing to Map Disease Processes Inside Atherosclerotic Plaques

This study generates a comprehensive single-cell transcriptomic atlas of human atherosclerosis including 118,578 high-quality cells from atherosclerotic coronary and carotid arteries. By performing systematic benchmarking of integration methods, we mitigated data overcorrection while separating major cell lineages. Notably, we define cell subtypes that have not been previously identified from individual human atherosclerosis scRNA-seq studies. Besides characterizing granular cell-type diversity and communication, we leverage this atlas to provide insights into smooth muscle cell (SMC) modulation. We integrate genome-wide association study data and uncover a critical role for modulated SMC phenotypes in CAD, myocardial infarction, and coronary calcification. Finally, we identify fibromyocyte/fibrochondrogenic SMC markers (LTBP1 and CRTAC1) as proxies of atherosclerosis progression and validate these through omics and spatial imaging analyses. Altogether, we create a unified atlas of human atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases. Link: https://doi.org/10.1016/j.celrep.2023.113380
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs