Single-Cell Transcriptomic Atlas of Different Human Cardiac Arteries Identifies Cell Types Associated With Vascular Physiology
Zhan Hu, Wendao Liu, Xiumeng Hua, Xiao Chen, Yuan Chang, Yiqing Hu, Zhenyu Xu, Jiangping Song
Abstract
Objective: Although cellular heterogeneity within arterial walls has been explored in mice and nonhuman primates, the cellular composition of human arterial walls remains unclear. Approach and Results: The cellular composition of nondiseased cardiac arteries (3 aortas, 2 pulmonary arteries and 9 coronary arteries) from 3 heart transplantation patients were investigated by single-cell sequencing of >10 5 cells. Clustering analysis identified 25 subpopulations representing the 10 main arterial cell types: vascular smooth muscle cell (4 clusters), fibroblast (4 clusters), macrophage (Mφ, 4 clusters), T cell (4 clusters), endothelial cell (4 clusters), NK cell (2 clusters), mast cell (1 cluster), myofibroblast (1 cluster), oligodendrocyte (1 cluster), and B/plasma cells (1 cluster). Vascular smooth muscle cell was the largest cell population in cardiac arteries, followed by fibroblast, Mφ, T cell, endothelial cell, NK cell, and so on. We compared cellular composition among different arteries and found some artery-specific vascular smooth muscle cell and fibroblast subpopulations. The communication between vascular smooth muscle cell and fibroblast was predominant in nondiseased condition. Atherosclerosis-associated genes were particularly enriched in endothelial cell and Mφ, and intercellular communication between endothelial cell and immune cells was predicted to increase in atherosclerosis. The interaction between ICAM1 / VCAM1 (EC1) and ITGB2 (immune cells, especially inflammatory Mφ) was speculated to be essential for the pathogenesis of atherosclerosis. Conclusions: We created a cell atlas of human nondiseased cardiac arteries, and characterized the cellular compositions in different cardiac arteries. Our results could be used as a reference to identify vascular disease-associated cell populations and help investigate new therapeutic strategies for vascular diseases.