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SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function.
Marchiano, Silvia; Hsiang, Tien-Ying; Khanna, Akshita; Higashi, Ty; Whitmore, Leanne S; Bargehr, Johannes; Davaapil, Hongorzul; Chang, Jean; Smith, Elise; Ong, Lay Ping; Colzani, Maria; Reinecke, Hans; Yang, Xiulan; Pabon, Lil; Sinha, Sanjay; Najafian, Behzad; Sniadecki, Nathan J; Bertero, Alessandro; Gale, Michael; Murry, Charles E.
  • Marchiano S; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
  • Hsiang TY; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
  • Khanna A; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
  • Higashi T; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
  • Whitmore LS; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
  • Bargehr J; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambrid
  • Davaapil H; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambrid
  • Chang J; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
  • Smith E; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.
  • Ong LP; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambrid
  • Colzani M; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambrid
  • Reinecke H; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
  • Yang X; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
  • Pabon L; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
  • Sinha S; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, ACCI Level 6, Box 110, Hills Road, Cambrid
  • Najafian B; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA.
  • Sniadecki NJ; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
  • Bertero A; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
  • Gale M; Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA. Electronic address: mgale@uw.edu.
  • Murry CE; Department of Laboratory Medicine and Pathology, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, USA; Center for Cardiovascular Biology, University of Washington, 850 Republican Street, Brotman Building, Seattle, WA 98109, USA; Institute for Stem Cell and Regenerative Medicine,
Stem Cell Reports ; 16(3): 478-492, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1082779
ABSTRACT
COVID-19 patients often develop severe cardiovascular complications, but it remains unclear if these are caused directly by viral infection or are secondary to a systemic response. Here, we examine the cardiac tropism of SARS-CoV-2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and smooth muscle cells (hPSC-SMCs). We find that that SARS-CoV-2 selectively infects hPSC-CMs through the viral receptor ACE2, whereas in hPSC-SMCs there is minimal viral entry or replication. After entry into cardiomyocytes, SARS-CoV-2 is assembled in lysosome-like vesicles and egresses via bulk exocytosis. The viral transcripts become a large fraction of cellular mRNA while host gene expression shifts from oxidative to glycolytic metabolism and upregulates chromatin modification and RNA splicing pathways. Most importantly, viral infection of hPSC-CMs progressively impairs both their electrophysiological and contractile function, and causes widespread cell death. These data support the hypothesis that COVID-19-related cardiac symptoms can result from a direct cardiotoxic effect of SARS-CoV-2.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Myocytes, Cardiac / Induced Pluripotent Stem Cells / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Stem Cell Reports Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Myocytes, Cardiac / Induced Pluripotent Stem Cells / SARS-CoV-2 / COVID-19 Limits: Humans Language: English Journal: Stem Cell Reports Year: 2021 Document Type: Article