SARS-CoV-2 infection induces beta cell transdifferentiation
Authors: Skyler Uhl
Vasuretha Chandar
Chengyang Liu
Shuibing Chen
J Jeya Vandana
Robert E Schwartz
Benjamin R tenOever
Angie Chi Nok Chong
Lauretta A Lacko
Tuo Zhang
Michael R Erdos
Yaron Bram
Jenny Xiang
Narisu Narisu
Dongxiang Xue
Lori L Bonnycastle
Joshua A Acklin
Xuming Tang
Ali Naji
Jean K Lim
Francis S Collins
Alain C Borczuk
Todd Evans
Bo Li
Zaw Min
Journal: Cell Metabolism (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: COVID-19; EgIF2; PRSS1; diabetes; human islets
Affiliations: Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA., 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., Genomics Resources Core Facility, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA., 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., The Center for Precision Health Research, National Human Genome Research Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA., Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA., Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA., Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA., Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA., Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. Electronic address: ., Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY 10029, USA. Electronic address: ., 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: ., Department of Surgery, Weill Cornell Medicine, 1300 York Avenue, New York, NY 10065, USA. Electronic address: .

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. 

Retracted: No

PubPeer comments:
 For some background about the scientific dispute surrounding this paper, see the guest posts by Dr Matthew Tenan on RetractionWatch: [part 1] , [part 2] and [part 3] . ,