{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:34:43Z","timestamp":1792154083373,"version":"4.4.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,9,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Ischemic stroke results in significant morbidity and mortality. By examining gene expression of cells comprising stroke clots, we aim to gain valuable insights into the underlying mechanisms of this disease and identify potential biomarkers of stroke cause.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We employed single\u2010cell RNA sequencing to analyze 10 clot samples from patients diagnosed with large vessel occlusion stroke. We aimed to identify and compare the immune cell compositions and gene expression profiles between stroke clots (atrial fibrillation vs carotid atherosclerosis). We also used Multi\u2010marker Analysis of Genomic Annotation and genome\u2010wide association studies summary statistics from the GIGASTROKE consortium to assess associations between genetic variants and cell type\u2010specific gene expression within the stroke subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Our analysis revealed distinct immune cell populations, including monocytes, macrophages, dendritic cells, neutrophils, and T cells in both clot types. Notably, we observed significant differences in gene expression within the mononuclear phagocytic system cells between clots from patients with atrial fibrillation and carotid atherosclerosis. We identified specific genes associated with atherosclerosis and stroke\u2010related processes, such as\n                      <jats:italic toggle=\"no\">CD74, HLA\u2010DRB1*01, HTRA1, C1Q, CD81<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"no\">CR1<\/jats:italic>\n                      from patients with carotid atherosclerosis. In atrial fibrillation clots, CD8 T cells and natural killer cells show upregulated expression of genes such as\n                      <jats:italic toggle=\"no\">GZMH<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">GZMB<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">S100A4<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">FCGBP2<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">HLA\u2010A<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">TIMP1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"no\">CLIC1<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"no\">IFITM2<\/jats:italic>\n                      , indicating their involvement in cytotoxic activities and potential tissue damage. The Multi\u2010marker Analysis of Genomic Annotation approach highlighted significant genetic associations within leukocytes underscoring the potential roles of B cells, T cells, and macrophages in clot pathogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">This study illuminates the immune and transcriptomic landscape within clots, offering potential biomarkers and lays the foundation for future research.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.041738","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T11:08:24Z","timestamp":1756465704000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Characterizing Stroke Clots Using Single\u2010Cell Sequencing"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4120-6649","authenticated-orcid":false,"given":"Daniela","family":"Renedo","sequence":"first","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]},{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanyeri","family":"Barak","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2032-8228","authenticated-orcid":false,"given":"Jonathan","family":"DeLong","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6497-5454","authenticated-orcid":false,"given":"Julian N.","family":"Acosta","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5857-5718","authenticated-orcid":false,"given":"Nanthiya","family":"Sujijantarat","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-649X","authenticated-orcid":false,"given":"Andrew","family":"Koo","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-1829","authenticated-orcid":false,"given":"Cyprien A.","family":"Rivier","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5377-434X","authenticated-orcid":false,"given":"Santiago","family":"Clocchiatti\u2010Tuozzo","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0119-7517","authenticated-orcid":false,"given":"Shufan","family":"Huo","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5147-1377","authenticated-orcid":false,"given":"Joseph","family":"Antonios","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3197-3062","authenticated-orcid":false,"given":"James","family":"Giles","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6407-0302","authenticated-orcid":false,"given":"Guido J.","family":"Falcone","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]},{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2003-5473","authenticated-orcid":false,"given":"Kevin N.","family":"Sheth","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]},{"name":"Yale School of Medicine","place":["New Haven, USA"]},{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Hebert","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Gunel","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6898-1680","authenticated-orcid":false,"given":"Lauren H.","family":"Sansing","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5431-8191","authenticated-orcid":false,"given":"Dhasakumar S.","family":"Navaratnam","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3234-9541","authenticated-orcid":false,"given":"Charles","family":"Matouk","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001123"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.0190"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.023314"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.23736\/S0390-5616.18.04629-5"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A4402"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn256"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0262413"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-022-01418-0"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.4132\/jptm.2022.12.12"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1874-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1140\/epjb\/e2013-40829-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23324-4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aah4573"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.09.025"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02458"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.048"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.07.007"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0276-y"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw377"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05165-3"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-05275-y"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11968-2"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11181-1"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0292-x"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-023-09265-w"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-023-00319-z"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu393"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mehy.2007.04.046"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.118.311577"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ancard.2014.12.004"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000065431.76788.D9"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1674"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.018984"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-20515-x"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.005038"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20080042"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000058404.92759.32"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-016-0152-y"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1189-3"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.042486"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.041738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:47:29Z","timestamp":1762930049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.041738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,2]]},"references-count":40,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2025,9,2]]}},"alternative-id":["10.1161\/JAHA.125.041738"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.041738","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,2]]},"assertion":[{"value":"2025-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eJAHA\/2025\/041738-T"}}