Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19

Kusmartseva Irina; Wu Wenting; Syed Farooq; Van Der Heide Verena; Jorgensen Marda; Joseph Paul; Tang Xiaohan; Candelario-Jalil Eduardo; Yang Changjun; Nick Harry; Harbert Jack L.; Posgai Amanda L.; Paulsen John David; Lloyd Richard; Cechin Sirlene; Pugliese Alberto; Campbell-Thompson Martha; Vander Heide Richard S.; Evans-Molina Carmella; Homann Dirk; Atkinson Mark A.

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Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19

机译：Covid-19胰腺供体和个人胰腺中SARS-COV-2进入因子的表达

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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.

机译：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感染与糖尿病诱导之间存在潜在关联，我们检测了胰腺血管紧张素转换酶2（ACE2）的表达，ACE2是SARS-CoV-2感染的关键进入因子。具体而言，我们分析了五个公共的scRNA-seq胰腺数据集，并对ACE2进行了荧光原位杂交、蛋白质印迹和免疫定位，并对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。这些电子和离体分析显示ACE2在胰腺导管上皮和微血管中显著表达，但我们发现在mRNA水平上内分泌细胞表达罕见。来自COVID-19个体的Pancreata表现出多个血栓性病变，SARS COV-2核衣壳蛋白表达主要限于导管。这些结果表明，通过ACE2感染胰腺内分泌细胞的SARS-CoV-2不太可能是新冠肺炎相关糖尿病的中心致病特征。

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《Cell metabolism》 |2020年第6期|共18页
作者
Kusmartseva Irina; Wu Wenting; Syed Farooq; Van Der Heide Verena; Jorgensen Marda; Joseph Paul; Tang Xiaohan; Candelario-Jalil Eduardo; Yang Changjun; Nick Harry; Harbert Jack L.; Posgai Amanda L.; Paulsen John David; Lloyd Richard; Cechin Sirlene; Pugliese Alberto; Campbell-Thompson Martha; Vander Heide Richard S.; Evans-Molina Carmella; Homann Dirk; Atkinson Mark A.;
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作者单位

Univ Florida Coll Med Inst Diabet Dept Pathol Immunol &

Lab Med Gainesville FL 32610 USA;

Indiana Univ Sch Med Ctr Diabet &

Metab Dis Indianapolis IN 46202 USA;

Indiana Univ Sch Med Ctr Diabet &

Metab Dis Indianapolis IN 46202 USA;

Icahn Sch Med Mt Sinai Dept Med Diabet Obes &

Metab Inst New York NY 10029 USA;

Univ Florida Coll Med Inst Diabet Dept Pathol Immunol &

Lab Med Gainesville FL 32610 USA;

Univ Florida Coll Med Inst Diabet Dept Pathol Immunol &

Lab Med Gainesville FL 32610 USA;

Univ Florida Coll Med Inst Diabet Dept Pathol Immunol &

Lab Med Gainesville FL 32610 USA;

Univ Florida Coll Med Dept Neurosci Gainesville FL 32601 USA;

Univ Florida Coll Med Dept Neurosci Gainesville FL 32601 USA;

Univ Florida Coll Med Dept Neurosci Gainesville FL 32601 USA;

Louisiana State Univ Dept Pathol New Orleans LA 70112 USA;

Univ Florida Coll Med Inst Diabet Dept Pathol Immunol &

Lab Med Gainesville FL 32610 USA;

Icahn Sch Med Mt Sinai Dept Pathol Mol &

Cell Based Med New York NY 10029 USA;

Baylor Coll Med Dept Virol &

Microbiol Houston TX 77030 USA;

Univ Miami Miller Sch Med Diabet Res Inst Dept Med Div Endocrinol Diabet &

Metab Dept Micro;

Univ Miami Miller Sch Med Diabet Res Inst Dept Med Div Endocrinol Diabet &

Metab Dept Micro;

Univ Florida Coll Med Inst Diabet Dept Pathol Immunol &

Lab Med Gainesville FL 32610 USA;

Louisiana State Univ Dept Pathol New Orleans LA 70112 USA;

Indiana Univ Sch Med Ctr Diabet &

Metab Dis Indianapolis IN 46202 USA;

Icahn Sch Med Mt Sinai Dept Med Diabet Obes &

Metab Inst New York NY 10029 USA;

Univ Florida Coll Med Inst Diabet Dept Pathol Immunol &

Lab Med Gainesville FL 32610 USA;

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正文语种 eng
中图分类内分泌腺疾病及代谢病;
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3. Adenoviral-mediated localized CTLA-4Ig gene expression induces long-term allograft pancreas survival and donor-specific immune tolerance in rats [J] . 中国人民解放军军医大学学报（英文版） . 2008,第006期
4. Expression of SARS-CoV-2 Host Cell Entry Factors in Immune System Components of Healthy Individuals and Its Relevance for COVID-19 Immunopathology [J] . Kumar Ashutosh, Kumar Sujeet, Narayan Ravi K., Viral immunology . 2021,第5期

机译：SARS-COV-2宿主细胞进入因子在健康个体免疫系统组分中的表达及其对Covid-19免疫病理学的相关性
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机译：SARS-COV-2细胞进入因子ACE2和TMPRSS2在人胰腺的微血管结构和管道中表达，但不富集β细胞
6. COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation [J] . Mohamed M. Aboudounya, Richard J. Heads Mediators of inflammation . 2021,第a期

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Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19

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