SARS-CoV-2 infection induces beta cell transdifferentiation.
SARS-CoV-2 infection induces beta cell transdifferentiation.
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DOI：
10.1016/j.cmet.2021.05.015
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发表时间：
2021-08-03
期刊：
影响因子：
29
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Tang X;Uhl S;Zhang T;Xue D;Li B;Vandana JJ;Acklin JA;Bonnycastle LL;Narisu N;Erdos MR;Bram Y;Chandar V;Chong ACN;Lacko LA;Min Z;Lim JK;Borczuk AC;Xiang J;Naji A;Collins FS;Evans T;Liu C;tenOever BR;Schwartz RE;Chen S
最近的临床数据表明，2019冠状病毒病（COVID-19）与糖尿病之间存在相关性。在这里，我们描述了在COVID-19个体尸检样本中胰腺β细胞中检测SARS-CoV-2病毒抗原。来自体外感染的单细胞RNA测序和免疫染色证实，多种类型的胰岛细胞对SARS-CoV-2敏感，引起细胞应激反应和趋化因子的诱导。在SARS-CoV-2感染后，β细胞显示出胰岛素的较低表达和α和腺泡细胞标志物的较高表达，分别包括胰高血糖素和胰蛋白酶1，表明细胞转分化。轨迹分析表明，SARS-CoV-2诱导eIF 2通路介导的β细胞转分化，这是一种可以用反式整合应激反应抑制剂（trans-ISRIB）逆转的表型。总之，这项研究证明了SARS-CoV-2感染导致细胞命运改变的一个例子，这为进一步了解COVID-19的病理机制提供了依据。在COVID-19受试者尸检的β细胞中检测到SARS-CoV-2病毒抗原SARS-CoV-2感染引起β细胞转分化SARS-CoV-2诱导的β细胞转分化由eIF 2途径介导Trans-ISRIB逆转SARS-CoV-2感染诱导的β细胞转分化报告了在COVID-19受试者尸检样本中检测到SARS-CoV-2病毒抗原。此外，SARS-CoV-2感染诱导eIF 2途径介导的β细胞转分化，这是一种可以被trans-ISRIB逆转的表型。
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. 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.
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DOI：
10.1126/science.abd3072
发表时间：
2020-11-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Daly JL;Simonetti B;Klein K;Chen KE;Williamson MK;Antón-Plágaro C;Shoemark DK;Simón-Gracia L;Bauer M;Hollandi R;Greber UF;Horvath P;Sessions RB;Helenius A;Hiscox JA;Teesalu T;Matthews DA;Davidson AD;Collins BM;Cullen PJ;Yamauchi Y
通讯作者：
Yamauchi Y
影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
影响因子：
64.5
作者：
Enge M;Arda HE;Mignardi M;Beausang J;Bottino R;Kim SK;Quake SR
通讯作者：
Quake SR
影响因子：
29
作者：
Coate KC;Cha J;Shrestha S;Wang W;Gonçalves LM;Almaça J;Kapp ME;Fasolino M;Morgan A;Dai C;Saunders DC;Bottino R;Aramandla R;Jenkins R;Stein R;Kaestner KH;Vahedi G;HPAP Consortium;Brissova M;Powers AC
通讯作者：
Powers AC
影响因子：
9.3
作者：
Baron M;Veres A;Wolock SL;Faust AL;Gaujoux R;Vetere A;Ryu JH;Wagner BK;Shen-Orr SS;Klein AM;Melton DA;Yanai I
通讯作者：
Yanai I