tetano
Editor, Senior Moderator
Cell Metab
. 2021 May 19;S1550-4131(21)00232-1.
doi: 10.1016/j.cmet.2021.05.015. Online ahead of print.
SARS-CoV-2 infection induces beta cell transdifferentiation
Xuming Tang[SUP] 1 [/SUP], Skyler Uhl[SUP] 2 [/SUP], Tuo Zhang[SUP] 3 [/SUP], Dongxiang Xue[SUP] 1 [/SUP], Bo Li[SUP] 1 [/SUP], J Jeya Vandana[SUP] 4 [/SUP], Joshua A Acklin[SUP] 2 [/SUP], Lori L Bonnycastle[SUP] 5 [/SUP], Narisu Narisu[SUP] 5 [/SUP], Michael R Erdos[SUP] 5 [/SUP], Yaron Bram[SUP] 6 [/SUP], Vasuretha Chandar[SUP] 6 [/SUP], Angie Chi Nok Chong[SUP] 1 [/SUP], Lauretta A Lacko[SUP] 1 [/SUP], Zaw Min[SUP] 7 [/SUP], Jean K Lim[SUP] 8 [/SUP], Alain C Borczuk[SUP] 9 [/SUP], Jenny Xiang[SUP] 3 [/SUP], Ali Naji[SUP] 7 [/SUP], Francis S Collins[SUP] 5 [/SUP], Todd Evans[SUP] 1 [/SUP], Chengyang Liu[SUP] 10 [/SUP], Benjamin R tenOever[SUP] 11 [/SUP], Robert E Schwartz[SUP] 12 [/SUP], Shuibing Chen[SUP] 13 [/SUP]
Affiliations
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.
Keywords: COVID-19; EgIF2; PRSS1; diabetes; human islets; insulin; trypsin 1.
. 2021 May 19;S1550-4131(21)00232-1.
doi: 10.1016/j.cmet.2021.05.015. Online ahead of print.
SARS-CoV-2 infection induces beta cell transdifferentiation
Xuming Tang[SUP] 1 [/SUP], Skyler Uhl[SUP] 2 [/SUP], Tuo Zhang[SUP] 3 [/SUP], Dongxiang Xue[SUP] 1 [/SUP], Bo Li[SUP] 1 [/SUP], J Jeya Vandana[SUP] 4 [/SUP], Joshua A Acklin[SUP] 2 [/SUP], Lori L Bonnycastle[SUP] 5 [/SUP], Narisu Narisu[SUP] 5 [/SUP], Michael R Erdos[SUP] 5 [/SUP], Yaron Bram[SUP] 6 [/SUP], Vasuretha Chandar[SUP] 6 [/SUP], Angie Chi Nok Chong[SUP] 1 [/SUP], Lauretta A Lacko[SUP] 1 [/SUP], Zaw Min[SUP] 7 [/SUP], Jean K Lim[SUP] 8 [/SUP], Alain C Borczuk[SUP] 9 [/SUP], Jenny Xiang[SUP] 3 [/SUP], Ali Naji[SUP] 7 [/SUP], Francis S Collins[SUP] 5 [/SUP], Todd Evans[SUP] 1 [/SUP], Chengyang Liu[SUP] 10 [/SUP], Benjamin R tenOever[SUP] 11 [/SUP], Robert E Schwartz[SUP] 12 [/SUP], Shuibing Chen[SUP] 13 [/SUP]
Affiliations
- PMID: 34081913
- PMCID: PMC8133495
- DOI: 10.1016/j.cmet.2021.05.015
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.
Keywords: COVID-19; EgIF2; PRSS1; diabetes; human islets; insulin; trypsin 1.