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10.1016/j.stemcr.2021.02.008

http://scihub22266oqcxt.onion/10.1016/j.stemcr.2021.02.008
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33657418!7881699!33657418
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suck abstract from ncbi


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pmid33657418      Stem+Cell+Reports 2021 ; 16 (3): 478-492
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  • SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function #MMPMID33657418
  • Marchiano S; Hsiang TY; Khanna A; Higashi T; Whitmore LS; Bargehr J; Davaapil H; Chang J; Smith E; Ong LP; Colzani M; Reinecke H; Yang X; Pabon L; Sinha S; Najafian B; Sniadecki NJ; Bertero A; Gale M Jr; Murry CE
  • Stem Cell Reports 2021[Mar]; 16 (3): 478-492 PMID33657418show ga
  • 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.
  • |COVID-19/*virology[MESH]
  • |Cells, Cultured[MESH]
  • |Humans[MESH]
  • |Induced Pluripotent Stem Cells/*virology[MESH]
  • |Myocytes, Cardiac/*virology[MESH]
  • |RNA Splicing/genetics[MESH]
  • |RNA, Messenger/genetics[MESH]
  • |SARS-CoV-2/genetics/*pathogenicity[MESH]


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