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SARS-CoV-2 infection induces beta cell transdifferentiation.
Tang, Xuming; Uhl, Skyler; Zhang, Tuo; Xue, Dongxiang; Li, Bo; Vandana, J Jeya; Acklin, Joshua A; Bonnycastle, Lori L; Narisu, Narisu; Erdos, Michael R; Bram, Yaron; Chandar, Vasuretha; Chong, Angie Chi Nok; Lacko, Lauretta A; Min, Zaw; Lim, Jean K; Borczuk, Alain C; Xiang, Jenny; Naji, Ali; Collins, Francis S; Evans, Todd; Liu, Chengyang; tenOever, Benjamin R; Schwartz, Robert E; Chen, Shuibing.
  • Tang X; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Uhl S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA.
  • Zhang T; Genomics Resources Core Facility, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Xue D; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Li B; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Vandana JJ; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Tri-Institutional PhD Program in Chemical Biology, Weill Cornell Medicine, the Rockefeller University, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Acklin JA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA.
  • Bonnycastle LL; The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
  • Narisu N; The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
  • Erdos MR; The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
  • Bram Y; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Chandar V; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Chong ACN; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Lacko LA; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Min Z; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Lim JK; Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA.
  • Borczuk AC; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Xiang J; Genomics Resources Core Facility, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Naji A; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
  • Collins FS; The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
  • Evans T; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
  • Liu C; Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Electronic address: chliu@pennmedicine.upenn.edu.
  • tenOever BR; Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA. Electronic address: benjamin.tenoever@mssm.edu.
  • Schwartz RE; Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA; Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: rec2025@med.cornell
  • Chen S; Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.
Cell Metab ; 33(8): 1577-1591.e7, 2021 08 03.
Article in English | MEDLINE | ID: covidwho-1240259
ABSTRACT
Recent clinical data have suggested a correlation between coronavirus disease 2019 (COVID-19) and diabetes. Here, we describe the detection of SARS-CoV-2 viral antigen in pancreatic beta cells in autopsy samples from individuals with COVID-19. Single-cell RNA sequencing and immunostaining from ex vivo infections confirmed that multiple types of pancreatic islet cells were susceptible to SARS-CoV-2, eliciting a cellular stress response and the induction of chemokines. Upon SARS-CoV-2 infection, beta cells showed a lower expression of insulin and a higher expression of alpha and acinar cell markers, including glucagon and trypsin1, respectively, suggesting cellular transdifferentiation. Trajectory analysis indicated that SARS-CoV-2 induced eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that could be reversed with trans-integrated stress response inhibitor (trans-ISRIB). Altogether, this study demonstrates an example of SARS-CoV-2 infection causing cell fate change, which provides further insight into the pathomechanisms of COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Insulin-Secreting Cells / Cell Transdifferentiation / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adolescent / Adult / Aged / Animals / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Cell Metab Journal subject: Metabolism Year: 2021 Document Type: Article Affiliation country: J.cmet.2021.05.015

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Insulin-Secreting Cells / Cell Transdifferentiation / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adolescent / Adult / Aged / Animals / Female / Humans / Male / Middle aged / Young adult Language: English Journal: Cell Metab Journal subject: Metabolism Year: 2021 Document Type: Article Affiliation country: J.cmet.2021.05.015