当前位置: X-MOL 学术Cell Metab. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19
Cell Metabolism ( IF 27.7 ) Pub Date : 2020-11-13 , DOI: 10.1016/j.cmet.2020.11.005
Irina Kusmartseva 1 , Wenting Wu 2 , Farooq Syed 3 , Verena Van Der Heide 4 , Marda Jorgensen 1 , Paul Joseph 1 , Xiaohan Tang 5 , Eduardo Candelario-Jalil 6 , Changjun Yang 6 , Harry Nick 6 , Jack L Harbert 7 , Amanda L Posgai 1 , John David Paulsen 8 , Richard Lloyd 9 , Sirlene Cechin 10 , Alberto Pugliese 10 , Martha Campbell-Thompson 11 , Richard S Vander Heide 7 , Carmella Evans-Molina 12 , Dirk Homann 4 , Mark A Atkinson 13
Affiliation  

Diabetes is associated with increased mortality from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given literature suggesting a potential association between SARS-CoV-2 infection and diabetes induction, we examined pancreatic expression of angiotensin-converting enzyme 2 (ACE2), the key entry factor for SARS-CoV-2 infection. Specifically, we analyzed five public scRNA-seq pancreas datasets and performed fluorescence in situ hybridization, western blotting, and immunolocalization for ACE2 with extensive reagent validation on normal human pancreatic tissues across the lifespan, as well as those from coronavirus disease 2019 (COVID-19) cases. These in silico and ex vivo analyses demonstrated prominent expression of ACE2 in pancreatic ductal epithelium and microvasculature, but we found rare endocrine cell expression at the mRNA level. Pancreata from individuals with COVID-19 demonstrated multiple thrombotic lesions with SARS-CoV-2 nucleocapsid protein expression that was primarily limited to ducts. These results suggest SARS-CoV-2 infection of pancreatic endocrine cells, via ACE2, is an unlikely central pathogenic feature of COVID-19-related diabetes.



中文翻译:


正常器官捐献者和 COVID-19 患者胰腺中 SARS-CoV-2 进入因子的表达



糖尿病与严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 死亡率增加有关。鉴于文献表明 SARS-CoV-2 感染与糖尿病诱发之间存在潜在关联,我们检查了血管紧张素转换酶 2 (ACE2) 的胰腺表达,ACE2 是 SARS-CoV-2 感染的关键进入因子。具体来说,我们分析了五个公共 scRNA-seq 胰腺数据集,并对整个生命周期的正常人胰腺组织以及 2019 年冠状病毒病 (COVID-19) 的胰腺组织进行了荧光原位杂交、蛋白质印迹和 ACE2 免疫定位,并进行了广泛的试剂验证。 )案例。这些计算机模拟离体分析表明,ACE2 在胰腺导管上皮和微脉管系统中显着表达,但我们发现内分泌细胞在 mRNA 水平上表达很少。 COVID-19 患者的胰腺表现出多处血栓性病变,其中 SARS-CoV-2 核衣壳蛋白表达主要局限于导管。这些结果表明,SARS-CoV-2 通过 ACE2 感染胰腺内分泌细胞,不太可能是 COVID-19 相关糖尿病的核心致病特征。

更新日期:2020-12-01
down
wechat
bug