SARS-CoV-2 infection induces beta cell transdifferentiation

• Published in: Cell metabolism Vol. 33; no. 8; pp. 1577 - 1591.e7
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.08.2021; Cell Press
• Subjects: Acetamides - pharmacology; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Cell Transdifferentiation - drug effects; Chlorocebus aethiops; Clinical and Translational Report; COVID-19; COVID-19 - mortality; COVID-19 - virology; Cyclohexylamines - pharmacology; Cytokines - metabolism; diabetes; EgIF2; Eukaryotic Initiation Factor-2 - metabolism; Female; Glucagon; Host-Pathogen Interactions; human islets; Humans; insulin; Insulin - metabolism; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Insulin-Secreting Cells - virology; Male; Middle Aged; Phenotype; PRSS1; SARS-CoV-2 - pathogenicity; Signal Transduction; Tissue Culture Techniques; Trypsin - metabolism; trypsin 1; Vero Cells; Young Adult; COVID-19; PRSS1; insulin; human islets; trypsin 1; diabetes; EgIF2
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2021.05.015

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. [Display omitted] •SARS-CoV-2 viral antigen is detected in beta cells of autopsies of COVID-19 subjects•SARS-CoV-2 infection causes beta cell transdifferentiation•SARS-CoV-2-induced beta cell transdifferentiation is mediated by eIF2 pathway•Trans-ISRIB reverses SARS-CoV-2 infection-induced beta cell transdifferentiation Here, Tang et al. reported the detection of SARS-CoV-2 viral antigen in autopsy samples from COVID-19 subjects. In addition, SARS-CoV-2 infection induces eIF2-pathway-mediated beta cell transdifferentiation, a phenotype that can be reversed by trans-ISRIB.