biostudies-literatureKalluri ASNHLBI NIH HHSNIGMS NIH HHS147-163https://www.ebi.ac.uk/biostudies/studies/S-EPMC6693656biostudies-literatureUnknown140(2)<h4>Background</h4>The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations.<h4>Methods</h4>We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells.<h4>Results</h4>Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for Vcam1 and Cd36 demonstrates regional heterogeneity in EC populations throughout the aorta.<h4>Conclusions</h4>We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease-relevant functions.CirculationSingle-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations.PMC6693656K08 HL128810R01 HL127564K24 HL105780T32 GM007753T32 GM008313R01 HL092577R01 GM049039R01 HL128914Edelman ERKalluri ASKathiresan SRegev AVellarikkal SKGupta RMEllinor PTSubramanian ANguyen LfalseSingle-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations.<h4>Background</h4>The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations.<h4>Methods</h4>We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells.<h4>Results</h4>Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for Vcam1 and Cd36 demonstrates regional heterogeneity in EC populations throughout the aorta.<h4>Conclusions</h4>We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease-relevant functions.2019-01-01T00:00:00Z2019 Jul2024-02-15T22:22:25.363Z2020-09-11T07:08:46ZS-EPMC66936563114658510.1161/circulationaha.118.03836210.1161/CIRCULATIONAHA.118.038362