{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:02:03Z","timestamp":1791388923956,"version":"4.3.3"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    <jats:bold>Purpose:<\/jats:bold>\n                    This study aims to illustrate the cellular landscape in the aorta of experimental aortic dissection (AD) and elaborate on the\n                    <jats:bold>smooth muscle cells (<\/jats:bold>\n                    SMCs\n                    <jats:bold>) heterogeneity<\/jats:bold>\n                    and functions among various cell types.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Male Apolipoprotein deficient (ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice at 28\u00a0weeks of age were infused with Ang II (2,500\u00a0ng\/kg\/min) to induce AD. Aortas from euthanized mice were harvested after 7\u00a0days for 10\u00d7Genomics single-cell RNA sequencing (scRNA-seq), followed by the identification of cell types and differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    AD was successfully induced in ApoE\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. scRNA-seq identified 15 cell clusters and nine cell types, including non-immune cells (endothelials, fibroblasts, and SMCs) and immune cells (B cells, natural killer T cell, macrophages, dendritic cells, neutrophils, and mast cells). The relative numbers of SMCs were remarkably changed, and seven core DEGs (ACTA2,IL6,CTGF,BGN,ITGA8,THBS1, and CDH5) were identified in SMCs. Moreover, we found SMCs can differentiate into 8 different subtypes through single-cell trajectory analysis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    scRNA-seq technology can successfully identify unique cell composition in experimental AD. To our knowledge, this is the first study that provided the complete cellular landscape in AD tissues from mice, seven core DEGs and eight subtypes of SMCs were identified, and the SMCs have evolution from matrix type to inflammatory type.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2022.836593","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T05:36:22Z","timestamp":1660196182000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Single-Cell RNA Sequencing Reveals Smooth Muscle Cells Heterogeneity in Experimental Aortic Dissection"],"prefix":"10.3389","volume":"13","author":[{"given":"Cheng","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxin","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui Chong","family":"Lau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danlei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoman","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haili","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohui","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijiang","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1038\/s41590-018-0276-y","article-title":"Reference-based Analysis of Lung Single-Cell Sequencing Reveals a Transitional Profibrotic Macrophage","volume":"20","author":"Aran","year":"2019","journal-title":"Nat. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"20170327","DOI":"10.1098\/rsif.2017.0327","article-title":"Differential Cell-Matrix Mechanoadaptations and Inflammation Drive Regional Propensities to Aortic Fibrosis, Aneurysm or Dissection in Hypertension","volume":"14","author":"Bersi","year":"2017","journal-title":"J. R. Soc. Interface"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1111\/jcmm.14137","article-title":"An Integrative Systems Approach Identifies Novel Candidates in Marfan Syndrome\u2010related Pathophysiology","volume":"23","author":"Bhushan","year":"2019","journal-title":"J. Cell. Mol. Medi"},{"key":"B4","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.forsciint.2011.07.006","article-title":"Aortic Dissecting Aneurysms-Hhistopathological Findings","volume":"214","author":"Bode-J\u00e4nisch","year":"2012","journal-title":"Forensic Sci. Int."},{"key":"B5","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","article-title":"Integrating Single-Cell Transcriptomic Data across Different Conditions, Technologies, and Species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1042\/cs20080235","article-title":"Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Is Present in Smooth Muscle Cells of Human Aneurysmal Aorta and Is Induced by Angiotensin II In Vitro","volume":"116","author":"Chen","year":"2009","journal-title":"Clin. Sci. (Lond)"},{"key":"B7","doi-asserted-by":"publisher","first-page":"S11","DOI":"10.1186\/1752-0509-8-S4-S11","article-title":"cytoHubba: Identifying Hub Objects and Sub-networks from Complex Interactome","author":"Chin","year":"2014","journal-title":"BMC Syst. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1186\/s12881-017-0505-5","article-title":"ACTA2 Mutation and Postpartum Hemorrhage: a Case Report","volume":"18","author":"Cooper","year":"2017","journal-title":"BMC Med. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"622","DOI":"10.3109\/07853890.2010.518156","article-title":"Inflammation and Immune Response in Acute Aortic Dissection","volume":"42","author":"Del Porto","year":"2010","journal-title":"Ann. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2048","DOI":"10.1074\/mcp.m110.001693","article-title":"Proteomics Characterization of Extracellular Space Components in the Human Aorta","volume":"9","author":"Didangelos","year":"2010","journal-title":"Mol. Cell. Proteomics"},{"key":"B11","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1161\/circulationaha.113.005062","article-title":"Endothelial Cell-specific Reactive Oxygen Species Production Increases Susceptibility to Aortic Dissection","volume":"129","author":"Fan","year":"2014","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"14371","DOI":"10.1016\/s0021-9258(18)98694-1","article-title":"Human Biglycan Gene. Putative Promoter, Intron-Exon Junctions, and Chromosomal Localization","volume":"266","author":"Fisher","year":"1991","journal-title":"J. Biol. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1093\/bib\/bbr042","article-title":"Phylogenetic-based Propagation of Functional Annotations within the Gene Ontology Consortium","volume":"12","author":"Gaudet","year":"2011","journal-title":"Briefings Bioinforma."},{"key":"B14","doi-asserted-by":"publisher","first-page":"w14489","DOI":"10.4414\/smw.2017.14489","article-title":"Acute Aortic Dissection: Pathogenesis, Risk Factors and Diagnosis","volume":"147","author":"Gawinecka","year":"2017","journal-title":"Swiss Med. Wkly."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/j.cell.2018.02.001","article-title":"Mapping the Mouse Cell Atlas by Microwell-Seq","volume":"172","author":"Han","year":"2018","journal-title":"Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41586-020-2157-4","article-title":"Construction of a Human Cell Landscape at Single-Cell Level","volume":"581","author":"Han","year":"2020","journal-title":"Nature"},{"key":"B17","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1016\/j.cell.2020.01.015","article-title":"Single-Cell Transcriptome Atlas of Murine Endothelial Cells","volume":"180","author":"Kalucka","year":"2020","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1038\/s41591-018-0096-5","article-title":"Phenotype Molding of Stromal Cells in the Lung Tumor Microenvironment","volume":"24","author":"Lambrechts","year":"2018","journal-title":"Nat. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"4455","DOI":"10.3892\/mmr.2017.7169","article-title":"Curcumin Attenuates the Development of Thoracic Aortic Aneurysm by Inhibiting VEGF Expression and Inflammation","volume":"16","author":"Li","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"B20","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.ebiom.2019.09.041","article-title":"Macrophage Metabolic Reprogramming Aggravates Aortic Dissection through the HIF1\u03b1-ADAM17 Pathway\u2730","volume":"49","author":"Lian","year":"2019","journal-title":"EBioMedicine"},{"key":"B21","doi-asserted-by":"publisher","first-page":"682","DOI":"10.3390\/antiox10050682","article-title":"Hydrogen Sulfide Attenuates Aortic Remodeling in Aortic Dissection Associating with Moderated Inflammation and Oxidative Stress through a NO-dependent Pathway","volume":"10","author":"Lu","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1093\/neuonc\/not029","article-title":"CDH5 Is Specifically Activated in Glioblastoma Stemlike Cells and Contributes to Vasculogenic Mimicry Induced by Hypoxia","volume":"15","author":"Mao","year":"2013","journal-title":"Neuro-Oncology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s12079-017-0409-3","article-title":"The Pro-fibrotic Connective Tissue Growth Factor (CTGF\/CCN2) Correlates with the Number of Necrotic-Regenerative Foci in Dystrophic Muscle","volume":"12","author":"Morales","year":"2018","journal-title":"J. Cell Commun. Signal."},{"key":"B24","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1083\/jcb.98.2.646","article-title":"Interactions of Thrombospondin with Extracellular Matrix Proteins: Selective Binding to Type V Collagen","volume":"98","author":"Mumby","year":"1984","journal-title":"J. Cell Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/0169-328x(91)90128-k","article-title":"Comparison of the Heat Shock Response in Cultured Cortical Neurons and Astrocytes","volume":"9","author":"Nishimura","year":"1991","journal-title":"Brain Res. Mol. Brain Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"198","DOI":"10.14348\/molcells.2018.2193","article-title":"Post-transcriptional Control of Tropoelastin in Aortic Smooth Muscle Cells Affects Aortic Dissection Onset","volume":"41","author":"Qi","year":"2018","journal-title":"Mol. Cells"},{"key":"B27","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.jacc.2018.04.089","article-title":"Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection","volume":"72","author":"Renard","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e17442","DOI":"10.1371\/journal.pone.0017442","article-title":"Genes and Gene Ontologies Common to Airflow Obstruction and Emphysema in the Lungs of Patients with COPD","volume":"6","author":"Savarimuthu Francis","year":"2011","journal-title":"PLoS One"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1308","DOI":"10.1161\/01.res.0000266662.98355.66","article-title":"Interaction of \u03b19\u03b21 Integrin with Thrombospondin-1 Promotes Angiogenesis","volume":"100","author":"Staniszewska","year":"2007","journal-title":"Circulation Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1016\/j.jvs.2016.02.063","article-title":"The Regulatory Role of Smooth Muscle 22 on the Proliferation of Aortic Smooth Muscle Cells Participates in the Development of Aortic Dissection","volume":"66","author":"Sun","year":"2017","journal-title":"J. Vasc. Surg."},{"key":"B31","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.avsg.2017.10.006","article-title":"Elevated Plasma Levels of LDL Cholesterol Promote Dissecting Thoracic Aortic Aneurysms in Angiotensin II-Induced Mice","volume":"48","author":"Tanaka","year":"2018","journal-title":"Ann. Vasc. Surg."},{"key":"B32","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s13023-019-1186-2","article-title":"European Reference Network for Rare Vascular Diseases (VASCERN) Consensus Statement for the Screening and Management of Patients with Pathogenic ACTA2 Variants","volume":"14","author":"van de Laar","year":"2019","journal-title":"Orphanet J. Rare Dis."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12979-016-0083-y","article-title":"A Pilot Observational Study on Magnesium and Calcium Imbalance in Elderly Patients with Acute Aortic Dissection","volume":"14","author":"Vianello","year":"2017","journal-title":"Immun. Ageing"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.1016\/j.jtcvs.2014.07.068","article-title":"Clinical Features of Acute Aortic Dissection from the Registry of Aortic Dissection in China","volume":"148","author":"Wang","year":"2014","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"B35","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fphys.2020.00054","article-title":"The Role of Macrophages in Aortic Dissection","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"114","DOI":"10.2174\/1570161115666170413145705","article-title":"Pharmacological Therapy of Abdominal Aortic Aneurysm: An Update","volume":"16","author":"Wang","year":"2018","journal-title":"Cvp"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e002476","DOI":"10.1161\/CIRCGEN.118.002476","article-title":"Clinical Implications of Identifying Pathogenic Variants in Individuals with Thoracic Aortic Dissection","volume":"12","author":"Wolford","year":"2019","journal-title":"Circ. Genom Precis. Med."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e2127587","DOI":"10.1001\/jamanetworkopen.2021.27587","article-title":"Association of Angiotensin II Type 1 Receptor Agonistic Autoantibodies with Outcomes in Patients with Acute Aortic Dissection","volume":"4","author":"Wu","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"B39","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R Package for Comparing Biological Themes Among Gene Clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS A J. Integr. Biol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"11","DOI":"10.14744\/AnatolJCardiol.2017.7839","article-title":"Aortic \u03b1-smooth Muscle Actin Expressions in Aortic Disorders and Coronary Artery Disease: An Immunohistochemical Study","volume":"19","author":"Yuan","year":"2018","journal-title":"Anatol. J. Cardiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1093\/cvr\/cvaa214","article-title":"Single-cell RNA Sequencing Reveals the Cellular Heterogeneity of Aneurysmal Infrarenal Abdominal Aorta","volume":"117","author":"Zhao","year":"2021","journal-title":"Cardiovasc Res."},{"key":"B42","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1186\/s12872-020-01652-5","article-title":"Predictors for the Development of Preoperative Oxygenation Impairment in Acute Aortic Dissection in Hypertensive Patients","volume":"20","author":"Zhao","year":"2020","journal-title":"BMC Cardiovasc Disord."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.836593\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T05:36:27Z","timestamp":1660196187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.836593\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,11]]},"references-count":42,"alternative-id":["10.3389\/fgene.2022.836593"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.836593","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,11]]},"article-number":"836593"}}