SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells.
SARS-CoV-2 Cell Entry Factors ACE2 and TMPRSS2 Are Expressed in the Microvasculature and Ducts of Human Pancreas but Are Not Enriched in β Cells.
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DOI：
10.1016/j.cmet.2020.11.006
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发表时间：
2020-12-01
期刊：
影响因子：
29
通讯作者：
Powers AC
中科院分区：
文献类型：
--
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
关于 COVID-19 患者新发糖尿病的孤立报告引发了这样的假设：SARS-CoV-2 对胰岛 β 细胞具有直接细胞毒性。这需要 SARS-CoV-2 通过其典型细胞进入因子、血管紧张素转换酶 2 (ACE2) 和跨膜丝氨酸蛋白酶 2 (TMPRSS2) 的共表达来结合并进入 β 细胞；然而，它们在人类胰腺中的表达尚未明确定义。我们分析了原代人胰岛细胞的六个转录数据集，发现 ACE2 和 TMPRSS2 并未在单个 β 细胞中共表达。在胰腺切片中，在患有和不患有糖尿病的捐赠者的β细胞中均未检测到ACE2和TMPRSS2蛋白。相反，ACE2 蛋白在胰岛和外分泌组织微脉管系统以及胰管子集中表达，而 TMPRSS2 蛋白仅限于导管细胞。这些发现降低了 SARS-CoV-2 通过 ACE2 和 TMPRSS2 直接感染体内 β 细胞的可能性。 ACE2 和 TMPRSS2 mRNA 在人胰腺中表达 ACE2 蛋白在一些胰岛和外分泌毛细血管和周细胞中表达 ACE2 和 TMPRSS2 蛋白在一些胰管中共表达 ACE2 和 TMPRSS2 蛋白在人胰腺 β 细胞中未检测到 Coate 等人。检查了人类胰腺中典型 SARS-CoV-2 进入蛋白 ACE2 和 TMPRSS2 的表达，并报告了微脉管系统（包括胰岛周细胞）中的 ACE2 表达，而 ACE2 和 TMPRSS2 在一些导管中都有表达。相反，在 β 细胞中未检测到这两种蛋白质，因此反对体内直接 β 细胞病毒感染。
Isolated reports of new-onset diabetes in individuals with COVID-19 have led to the hypothesis that SARS-CoV-2 is directly cytotoxic to pancreatic islet β cells. This would require binding and entry of SARS-CoV-2 into β cells via co-expression of its canonical cell entry factors, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2); however, their expression in human pancreas has not been clearly defined. We analyzed six transcriptional datasets of primary human islet cells and found that ACE2 and TMPRSS2 were not co-expressed in single β cells. In pancreatic sections, ACE2 and TMPRSS2 protein was not detected in β cells from donors with and without diabetes. Instead, ACE2 protein was expressed in islet and exocrine tissue microvasculature and in a subset of pancreatic ducts, whereas TMPRSS2 protein was restricted to ductal cells. These findings reduce the likelihood that SARS-CoV-2 directly infects β cells in vivo through ACE2 and TMPRSS2. ACE2 and TMPRSS2 mRNA are expressed in the human pancreas ACE2 protein is expressed in some islet and exocrine capillaries and pericytes ACE2 and TMPRSS2 proteins are co-expressed in some pancreatic ducts ACE2 and TMPRSS2 protein is not detected in β cells of the human pancreas Coate et al. examined expression of canonical SARS-CoV-2 entry proteins ACE2 and TMPRSS2 in the human pancreas and report ACE2 expression in the microvasculature, including islet pericytes, whereas both ACE2 and TMPRSS2 are expressed in some ducts. Conversely, neither protein is detected in β cells, arguing against direct β cell viral infection in vivo.
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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
影响因子：
5.1
作者：
Goldman, Nina;Fink, Douglas;Davies, Zoe
通讯作者：
Davies, Zoe
糖尿病中的β细胞功能障碍：胰岛微环境是一种不寻常的嫌疑犯。
影响因子：
8.2
作者：
Almaça J;Caicedo A;Landsman L
通讯作者：
Landsman L
影响因子：
5.2
作者：
Fignani D;Licata G;Brusco N;Nigi L;Grieco GE;Marselli L;Overbergh L;Gysemans C;Colli ML;Marchetti P;Mathieu C;Eizirik DL;Sebastiani G;Dotta F
通讯作者：
Dotta F
影响因子：
8.2
作者：
Cariou, Bertrand;Hadjadj, Samy;Gourdy, Pierre
通讯作者：
Gourdy, Pierre