SARS-CoV-2 infection induces beta cell transdifferentiation

Tang Xuming; Uhl Skyler; Zhang TuoXue DongxiangLi BoVandana J. JeyaAcklin Joshua A.Bonnycastle Lori L.Narisu NarisuErdos Michael R.Bram YaronChandar VasurethaChong Angie Chi NokLacko Lauretta A.Min ZawLim Jean K.Borczuk Alain C.Xiang JennyNaji AliCollins Francis S.Evans ToddLiu ChengyangTenOever Benjamin R.Schwartz Robert E.Chen Shuibing

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SARS-CoV-2 infection induces beta cell transdifferentiation

机译：SARS-CoV-2 infection induces beta cell transdifferentiation

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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 SARSCoV-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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《Cell metabolism》 |2021年第8期|1577-1591|共23页
作者
Tang Xuming; Uhl Skyler; Zhang TuoXue DongxiangLi BoVandana J. JeyaAcklin Joshua A.Bonnycastle Lori L.Narisu NarisuErdos Michael R.Bram YaronChandar VasurethaChong Angie Chi NokLacko Lauretta A.Min ZawLim Jean K.Borczuk Alain C.Xiang JennyNaji AliCollins Francis S.Evans ToddLiu ChengyangTenOever Benjamin R.Schwartz Robert E.Chen Shuibing;
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Weill Cornell Med, Dept Surg, 1300 York Ave, New York, NY 10065 USA;

Univ Penn, Dept Surg, Sch Med, Philadelphia, PA 19104 USA;

Icahn Sch Med Mt Sinai, Dept Microbiol, 1468 Madison Ave, New York, NY 10029 USAWeill Cornell Med, Dept Pathol & Lab Med, 1300 York Ave, New York, NY 10065 USAWeill Cornell Med, Genom Resources Core Facil, 1300 York Ave, New York, NY 10065 USANHGRI, Ctr Precis Hlth Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USAWeill Cornell Med, Div Gastroenterol & Hepatol, Dept Med, 1300 York Ave, New York, NY 10065 USA;

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正文语种英语
中图分类内分泌腺疾病及代谢病;
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SARS-CoV-2 infection induces beta cell transdifferentiation

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