Xuming Tang, Skyler Uhl, Tuo Zhang, Dongxiang Xue, Bo Li, J Jeya Vandana, Joshua A Acklin, Lori L Bonnycastle, Narisu Narisu, Michael R Erdos, Yaron Bram, Vasuretha Chandar, Angie Chi Nok Chong, Lauretta A Lacko, Zaw Min, Jean K Lim, Alain C Borczuk, Jenny Xiang, Ali Naji, Francis S Collins, Todd Evans, Chengyang Liu, Benjamin R tenOever, Robert E Schwartz, Shuibing Chen
Author Information
Xuming Tang: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Skyler Uhl: 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.
Tuo Zhang: Genomics Resources Core Facility, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Dongxiang Xue: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Bo Li: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
J Jeya Vandana: 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.
Joshua A Acklin: 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.
Lori L Bonnycastle: The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Narisu Narisu: The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Michael R Erdos: The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Yaron Bram: Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Vasuretha Chandar: Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Angie Chi Nok Chong: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Lauretta A Lacko: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Zaw Min: Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Jean K Lim: Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA.
Alain C Borczuk: Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Jenny Xiang: Genomics Resources Core Facility, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Ali Naji: Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Francis S Collins: The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Todd Evans: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA.
Chengyang Liu: Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Electronic address: chliu@pennmedicine.upenn.edu.
Benjamin R tenOever: Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA. Electronic address: benjamin.tenoever@mssm.edu.
Robert E Schwartz: 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.edu.
Shuibing Chen: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: shc2034@med.cornell.edu.
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.
