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Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis.
Mosquera, Jose Verdezoto; Auguste, Gaëlle; Wong, Doris; Turner, Adam W; Hodonsky, Chani J; Alvarez-Yela, Astrid Catalina; Song, Yipei; Cheng, Qi; Lino Cardenas, Christian L; Theofilatos, Konstantinos; Bos, Maxime; Kavousi, Maryam; Peyser, Patricia A; Mayr, Manuel; Kovacic, Jason C; Björkegren, Johan L M; Malhotra, Rajeev; Stukenberg, P Todd; Finn, Aloke V; van der Laan, Sander W; Zang, Chongzhi; Sheffield, Nathan C; Miller, Clint L.
Afiliação
  • Mosquera JV; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Auguste G; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Wong D; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Turner AW; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Hodonsky CJ; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA.
  • Alvarez-Yela AC; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
  • Song Y; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Computer Engineering, University of Virginia, Charlottesville, VA 22908, USA.
  • Cheng Q; CVPath Institute, Gaithersburg, MD 20878, USA.
  • Lino Cardenas CL; Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
  • Theofilatos K; King's British Heart Foundation Centre, King's College London, London WC2R 2LS, UK.
  • Bos M; Department of Epidemiology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
  • Kavousi M; Department of Epidemiology, Erasmus University Medical Center, 3000 CA Rotterdam, the Netherlands.
  • Peyser PA; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI 48019, USA.
  • Mayr M; King's British Heart Foundation Centre, King's College London, London WC2R 2LS, UK; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Kovacic JC; Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia; St. Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
  • Björkegren JLM; Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Medicine, Karolinska Institutet, 141 52 Huddinge, Sweden.
  • Malhotra R; Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.
  • Stukenberg PT; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA.
  • Finn AV; CVPath Institute, Gaithersburg, MD 20878, USA.
  • van der Laan SW; Central Diagnostics Laboratory, Division Laboratories, Pharmacy, and Biomedical Genetics, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.
  • Zang C; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA; Departme
  • Sheffield NC; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA; Departme
  • Miller CL; Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA; Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA; Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA; Departme
Cell Rep ; 42(11): 113380, 2023 11 28.
Article em En | MEDLINE | ID: mdl-37950869
Coronary artery disease (CAD) is characterized by atherosclerotic plaque formation in the arterial wall. CAD progression involves complex interactions and phenotypic plasticity among vascular and immune cell lineages. Single-cell RNA-seq (scRNA-seq) studies have highlighted lineage-specific transcriptomic signatures, but human cell phenotypes remain controversial. Here, we perform an integrated meta-analysis of 22 scRNA-seq libraries to generate a comprehensive map of human atherosclerosis with 118,578 cells. Besides characterizing granular cell-type diversity and communication, we leverage this atlas to provide insights into smooth muscle cell (SMC) modulation. We integrate genome-wide association study data and uncover a critical role for modulated SMC phenotypes in CAD, myocardial infarction, and coronary calcification. Finally, we identify fibromyocyte/fibrochondrogenic SMC markers (LTBP1 and CRTAC1) as proxies of atherosclerosis progression and validate these through omics and spatial imaging analyses. Altogether, we create a unified atlas of human atherosclerosis informing cell state-specific mechanistic and translational studies of cardiovascular diseases.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença da Artéria Coronariana / Aterosclerose / Placa Aterosclerótica / Infarto do Miocárdio Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Doença da Artéria Coronariana / Aterosclerose / Placa Aterosclerótica / Infarto do Miocárdio Idioma: En Ano de publicação: 2023 Tipo de documento: Article