Expression of SARS-CoV-2 Entry Factors in the Pancreas of Normal Organ Donors and Individuals with COVID-19
| Autor: | Eduardo Candelario-Jalil, Irina Kusmartseva, Verena van der Heide, Harry S. Nick, Richard S. Vander Heide, Farooq Syed, Mark A. Atkinson, Carmella Evans-Molina, Tang X, Dirk Homann, John David Paulsen, Martha Campbell-Thompson, Changjun Yang, Richard E. Lloyd, Wenting Wu, Amanda L. Posgai, Jack L. Harbert, Alberto Pugliese, Sirlene Cechin, Paul N. Joseph, Marda Jorgensen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty insulin Physiology type 1 diabetes viruses ACE2 Gene Expression Enteroendocrine cell Type 2 diabetes 03 medical and health sciences 0302 clinical medicine Short Article Diabetes mellitus Gene expression medicine Humans pancreas Molecular Biology TMPRSS2 Type 1 diabetes medicine.diagnostic_test islet business.industry SARS-CoV-2 Serine Endopeptidases COVID-19 Cell Biology Virus Internalization medicine.disease Tissue Donors Blot 030104 developmental biology medicine.anatomical_structure Diabetes Mellitus Type 2 type 2 diabetes CD34 Angiotensin-Converting Enzyme 2 Pancreas business 030217 neurology & neurosurgery Fluorescence in situ hybridization |
| Zdroj: | Cell Metabolism |
| ISSN: | 1932-7420 1550-4131 |
| Popis: | 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. Graphical Abstract Highlights • 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. |
| Databáze: | OpenAIRE |
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