Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.
Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19.
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DOI：
10.1016/j.cmet.2020.11.005
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发表时间：
2020-12-01
期刊：
影响因子：
29
通讯作者：
Atkinson MA
中科院分区：
文献类型：
--
作者：
Kusmartseva I;Wu W;Syed F;Van Der Heide V;Jorgensen M;Joseph P;Tang X;Candelario-Jalil E;Yang C;Nick H;Harbert JL;Posgai AL;Paulsen JD;Lloyd R;Cechin S;Pugliese A;Campbell-Thompson M;Vander Heide RS;Evans-Molina C;Homann D;Atkinson MA
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) 病例的胰腺组织进行了广泛的试剂验证，并对 ACE2 进行了荧光原位杂交、蛋白质印迹和免疫定位。这些计算机模拟和离体分析表明，ACE2 在胰腺导管上皮和微血管系统中显着表达，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，胰腺内分泌细胞通过 ACE2 感染 SARS-CoV-2，不太可能是 COVID-19 相关糖尿病的核心致病特征。 ACE2 mRNA 和蛋白质在人胰腺导管和微血管中表达 ACE2 mRNA 很少检测到，并且在人胰腺内分泌细胞中水平较低。胰腺 ACE2 蛋白表达在整个生命周期中发生变化，并与 BMI 相关。在 COVID-19 胰腺 Kusmartseva 等人的导管中检测到 SARS-CoV-2 NP，但在内分泌细胞中未检测到。表明 ACE2 在胰腺微血管和导管结构中优先表达，表明这些结构比胰岛内分泌细胞更可能成为 SARS-CoV-2 感染的目标。在 COVID-19 患者的胰腺导管上皮（而非内分泌细胞）中检测到 SARS-CoV-2 核衣壳蛋白支持了这一观点。
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. ACE2 mRNA and protein are expressed in human pancreatic ducts and microvasculature ACE2 mRNA was rarely detected and at low levels in human pancreatic endocrine cells Pancreatic ACE2 protein expression changes across the lifespan and correlates with BMI SARS-CoV-2 NP was detected in ducts, but not endocrine cells, of COVID-19 pancreata Kusmartseva et al. demonstrate preferential ACE2 expression in pancreatic microvascular and ductal structures, suggesting these constitute a more likely target than islet endocrine cells in SARS-CoV-2 infection. This notion was supported by detection of SARS-CoV-2 nucleocapsid protein in ductal epithelium, but not endocrine cells, of pancreata from individuals with COVID-19.
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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
影响因子：
5.1
作者：
Goldman, Nina;Fink, Douglas;Davies, Zoe
通讯作者：
Davies, Zoe
影响因子：
5.2
作者：
Mercatelli, Daniele;Giorgi, Federico M.
通讯作者：
Giorgi, Federico M.
影响因子：
44.5
作者：
Holman, Naomi;Knighton, Peter;Valabhji, Jonathan
通讯作者：
Valabhji, Jonathan