{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:34:43Z","timestamp":1791653683476,"version":"4.3.4"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We identified 25 cell populations, each with a unique multiomic signature, including macrophages, T cells, NK (natural killer) cells, mast cells, B cells, plasma cells, neutrophils, dendritic cells, endothelial cells, fibroblasts, and smooth muscle cells (SMCs). Among the macrophages, we identified 2 proinflammatory subsets enriched in IL-1B (interleukin-1B) or C1Q expression, 2 TREM2-positive foam cells (1 expressing inflammatory genes), and subpopulations with a proliferative gene signature and SMC-specific gene signature with fibrotic pathways upregulated. Further characterization revealed various subsets of SMCs and fibroblasts, including SMC-derived foam cells. These foamy SMCs were localized in the deep intima of coronary atherosclerotic lesions. Utilizing cellular indexing of transcriptomes and epitopes by sequencing data, we developed a flow cytometry panel, using cell surface proteins CD29, CD142, and CD90, to isolate SMC-derived cells from lesions. Lastly, we observed reduced proportions of efferocytotic macrophages, classically activated endothelial cells, and contractile and modulated SMC-derived cells, while inflammatory SMCs were enriched in plaques of clinically symptomatic versus asymptomatic patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Our multimodal atlas of cell populations within atherosclerosis provides novel insights into the diversity, phenotype, location, isolation, and clinical relevance of the unique cellular composition of human carotid atherosclerosis. These findings facilitate both the mapping of cardiovascular disease susceptibility loci to specific cell types and the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.123.320524","type":"journal-article","created":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T05:03:59Z","timestamp":1708578239000},"page":"930-945","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":117,"title":["High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1380-9242","authenticated-orcid":true,"given":"Alexander C.","family":"Bashore","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9227-1742","authenticated-orcid":true,"given":"Hanying","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia (H.Y., M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyi","family":"Xue","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-5377","authenticated-orcid":true,"given":"Lucie Y.","family":"Zhu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9749-9930","authenticated-orcid":true,"given":"Eunyoung","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Mawson","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9257-0849","authenticated-orcid":true,"given":"Johana","family":"Coronel","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2494-9179","authenticated-orcid":true,"given":"Allen","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8031-017X","authenticated-orcid":true,"given":"Nadja","family":"Sachs","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (N.S., L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Ho","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-5213","authenticated-orcid":true,"given":"Leila S.","family":"Ross","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Kissner","sequence":"additional","affiliation":[{"name":"Columbia Stem Cell Initiative, Department of Genetics and Development (M.K., E.P.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3516-297X","authenticated-orcid":true,"given":"Emmanuelle","family":"Passegu\u00e9","sequence":"additional","affiliation":[{"name":"Columbia Stem Cell Initiative, Department of Genetics and Development (M.K., E.P.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Bauer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5228-2634","authenticated-orcid":true,"given":"Lars","family":"Maegdefessel","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (N.S., L.M.)."},{"name":"German Center for Cardiovascular Research, Partner Site Munich Heart Alliance (L.M.)."},{"name":"Department of Medicine, Karolinksa Institute, Stockholm, Sweden (L.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2422-9494","authenticated-orcid":true,"given":"Mingyao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia (H.Y., M.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muredach P.","family":"Reilly","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY (A.C.B., C.X., L.Y.Z., E.K., T.M., J.C., A.C., S.H., L.S.R., R.C.B., M.P.R.)."},{"name":"Irving Institute for Clinical and Translational Research (M.P.R.), Columbia University Irving Medical Center, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03392-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.302721"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199705013361802"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.179739"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01233-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.237693"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0590-4"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316770"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.318974"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42256-022-00545-w"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.03.014"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00338-8"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-018-0029-z"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri910"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000255559.77687.c1"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M405432200"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-022-00042-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.187534"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7303"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.08.2148"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.317953"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.005015"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312434"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3866"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.311022"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.046672"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0512-5"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.312804"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.312509"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.316903"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048378"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.20900\/immunometab20210022"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318971"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjopen\/oeab043"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2021.11.025"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.36.1.1"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.07.007"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03341-5"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.122.317583"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1101\/2022.11.28.518255"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.124574"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3258"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.10.015"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvab260"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057789"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI82719"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11853"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6659"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.09.008"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehy124"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000183928.25844.f6"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.120.3.413"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1002\/biof.41"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4380"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1382-0"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.271874.120"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202170126"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06891-x"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8020251"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.123.320524","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T14:42:05Z","timestamp":1748529725000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.123.320524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4]]},"references-count":65,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4]]}},"alternative-id":["10.1161\/ATVBAHA.123.320524"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.123.320524","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.07.13.23292633","asserted-by":"object"}]},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4]]},"assertion":[{"value":"2023-12-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}