{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:42:47Z","timestamp":1792122167525,"version":"4.4.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,7,9]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>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 &gt;10\u2009000 cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              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\n              <jats:italic>Vcam1<\/jats:italic>\n              and\n              <jats:italic>Cd36<\/jats:italic>\n              demonstrates regional heterogeneity in EC populations throughout the aorta.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from &gt;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\u2013relevant functions.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.118.038362","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T09:00:16Z","timestamp":1559293216000},"page":"147-163","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":339,"title":["Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations"],"prefix":"10.1161","volume":"140","author":[{"given":"Aditya S.","family":"Kalluri","sequence":"first","affiliation":[{"name":"Broad Institute of MIT and Harvard University, Cambridge, MA (A.S.K., S.K.V., L.N., A.S., P.T.E., A.R., S.K., R.M.G.)."},{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge (A.S.K., E.R.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamsudheen K.","family":"Vellarikkal","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard University, Cambridge, MA (A.S.K., S.K.V., L.N., A.S., P.T.E., A.R., S.K., R.M.G.)."},{"name":"Center for Genomic Medicine (S.K.V., S.K., R.M.G.), Massachusetts General Hospital, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elazer R.","family":"Edelman","sequence":"additional","affiliation":[{"name":"Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge (A.S.K., E.R.E.)."},{"name":"Division of Cardiovascular Medicine, Department of Medicine (E.R.E., R.M.G.), Brigham and Women\u2019s Hospital, Boston MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard University, Cambridge, MA (A.S.K., S.K.V., L.N., A.S., P.T.E., A.R., S.K., R.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayshwarya","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard University, Cambridge, MA (A.S.K., S.K.V., L.N., A.S., P.T.E., A.R., S.K., R.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick T.","family":"Ellinor","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard University, Cambridge, MA (A.S.K., S.K.V., L.N., A.S., P.T.E., A.R., S.K., R.M.G.)."},{"name":"Cardiology Division, Department of Medicine (P.T.E., S.K.), Massachusetts General Hospital, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aviv","family":"Regev","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard University, Cambridge, MA (A.S.K., S.K.V., L.N., A.S., P.T.E., A.R., S.K., R.M.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sekar","family":"Kathiresan","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard University, Cambridge, MA (A.S.K., S.K.V., L.N., A.S., P.T.E., A.R., S.K., R.M.G.)."},{"name":"Cardiology Division, Department of Medicine (P.T.E., S.K.), Massachusetts General Hospital, Boston."},{"name":"Center for Genomic Medicine (S.K.V., S.K., R.M.G.), Massachusetts General Hospital, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajat M.","family":"Gupta","sequence":"additional","affiliation":[{"name":"Broad Institute of MIT and Harvard University, Cambridge, MA (A.S.K., S.K.V., L.N., A.S., P.T.E., A.R., S.K., R.M.G.)."},{"name":"Division of Cardiovascular Medicine, Department of Medicine (E.R.E., R.M.G.), Brigham and Women\u2019s Hospital, Boston MA."},{"name":"Division of Genetics (R.M.G.), Brigham and Women\u2019s Hospital, Boston MA."},{"name":"Center for Genomic Medicine (S.K.V., S.K., R.M.G.), Massachusetts General Hospital, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","first-page":"3527","article-title":"Endothelial cells in physiology and in the pathophysiology of vascular disorders.","volume":"91","author":"Cines DB","year":"1998","unstructured":"Cines, DB, Pollak, ES, Buck, CA, Loscalzo, J, Zimmerman, GA, McEver, RP, Pober, JS, Wick, TM, Konkle, BA, Schwartz, BS, Barnathan, ES, McCrae, KR, Hug, BA, Schmidt, AM, Stern, DM. 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