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Merck

SARS-CoV-2 infection induces beta cell transdifferentiation.

Cell metabolism (2021-06-04)
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
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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