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Pathogenic variants damage cell composition and single cell transcription in cardiomyopathies.
Reichart, Daniel; Lindberg, Eric L; Maatz, Henrike; Miranda, Antonio M A; Viveiros, Anissa; Shvetsov, Nikolay; Gärtner, Anna; Nadelmann, Emily R; Lee, Michael; Kanemaru, Kazumasa; Ruiz-Orera, Jorge; Strohmenger, Viktoria; DeLaughter, Daniel M; Patone, Giannino; Zhang, Hao; Woehler, Andrew; Lippert, Christoph; Kim, Yuri; Adami, Eleonora; Gorham, Joshua M; Barnett, Sam N; Brown, Kemar; Buchan, Rachel J; Chowdhury, Rasheda A; Constantinou, Chrystalla; Cranley, James; Felkin, Leanne E; Fox, Henrik; Ghauri, Ahla; Gummert, Jan; Kanda, Masatoshi; Li, Ruoyan; Mach, Lukas; McDonough, Barbara; Samari, Sara; Shahriaran, Farnoush; Yapp, Clarence; Stanasiuk, Caroline; Theotokis, Pantazis I; Theis, Fabian J; van den Bogaerdt, Antoon; Wakimoto, Hiroko; Ware, James S; Worth, Catherine L; Barton, Paul J R; Lee, Young-Ae; Teichmann, Sarah A; Milting, Hendrik; Noseda, Michela; Oudit, Gavin Y.
  • Reichart D; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Lindberg EL; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Maatz H; Department of Medicine I, University Hospital, LMU Munich, 80336 Munich, Germany.
  • Miranda AMA; Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
  • Viveiros A; Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
  • Shvetsov N; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10785 Berlin, Germany.
  • Gärtner A; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Nadelmann ER; British Heart Foundation Centre for Research Excellence and Centre for Regenerative Medicine, Imperial College London, London WC2R 2LS, UK.
  • Lee M; Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
  • Kanemaru K; Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
  • Ruiz-Orera J; Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
  • Strohmenger V; Erich and Hanna Klessmann Institute, Heart and Diabetes Center NRW, University Hospital of the Ruhr-University Bochum, 32545 Bad Oeynhausen, Germany.
  • DeLaughter DM; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Patone G; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Zhang H; Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
  • Woehler A; Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
  • Lippert C; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Kim Y; Walter-Brendel-Centre of Experimental Medicine, Ludwig-Maximilian University of Munich, 81377 Munich, Germany.
  • Adami E; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Gorham JM; Howard Hughes Medical Institute, Bethesda, MD 20815, USA.
  • Barnett SN; Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
  • Brown K; Division of Cardiology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
  • Buchan RJ; Mazankowski Alberta Heart Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta T6G 2R3, Canada.
  • Chowdhury RA; Systems Biology Imaging Platform, Berlin Institute for Medical Systems Biology (BIMSB), Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association (MDC), 10115 Berlin, Germany.
  • Constantinou C; Digital Health-Machine Learning group, Hasso Plattner Institute for Digital Engineering, University of Potsdam, 14482 Potsdam, Germany.
  • Cranley J; Hasso Plattner Institute for Digital Health, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Felkin LE; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Fox H; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Ghauri A; Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
  • Gummert J; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Kanda M; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Li R; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
  • Mach L; Cardiac Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
  • McDonough B; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Samari S; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London SW3 6NR, UK.
  • Shahriaran F; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Yapp C; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Stanasiuk C; Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
  • Theotokis PI; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Theis FJ; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London SW3 6NR, UK.
  • van den Bogaerdt A; Heart and Diabetes Center NRW, Clinic for Thoracic and Cardiovascular Surgery, University Hospital of the Ruhr-University, 32545 Bad Oeynhausen, Germany.
  • Wakimoto H; Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
  • Ware JS; Heart and Diabetes Center NRW, Clinic for Thoracic and Cardiovascular Surgery, University Hospital of the Ruhr-University, 32545 Bad Oeynhausen, Germany.
  • Worth CL; Cardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany.
  • Barton PJR; Department of Rheumatology and Clinical Immunology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
  • Lee YA; Cellular Genetics Programme, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton CB10 1SA, UK.
  • Teichmann SA; National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Milting H; Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust, London SW3 6NR, UK.
  • Noseda M; Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Oudit GY; Howard Hughes Medical Institute, Bethesda, MD 20815, USA.
Science ; 377(6606): eabo1984, 2022 08 05.
Article en En | MEDLINE | ID: mdl-35926050
ABSTRACT
Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized the transcriptome of 880,000 nuclei from 18 control and 61 failing, nonischemic human hearts with pathogenic variants in DCM and ACM genes or idiopathic disease. We performed genotype-stratified analyses of the ventricular cell lineages and transcriptional states. The resultant DCM and ACM ventricular cell atlas demonstrated distinct right and left ventricular responses, highlighting genotype-associated pathways, intercellular interactions, and differential gene expression at single-cell resolution. Together, these data illuminate both shared and distinct cellular and molecular architectures of human heart failure and suggest candidate therapeutic targets.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cardiomiopatía Dilatada / Displasia Ventricular Derecha Arritmogénica / Análisis de la Célula Individual / Transcriptoma / Insuficiencia Cardíaca Límite: Humans Idioma: En Año: 2022 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Cardiomiopatía Dilatada / Displasia Ventricular Derecha Arritmogénica / Análisis de la Célula Individual / Transcriptoma / Insuficiencia Cardíaca Límite: Humans Idioma: En Año: 2022 Tipo del documento: Article