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SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis

Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2, and NRP1 are express...

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Autores principales: Szlachcic, Wojciech J., Dabrowska, Agnieszka, Milewska, Aleksandra, Ziojla, Natalia, Blaszczyk, Katarzyna, Barreto-Duran, Emilia, Sanak, Marek, Surmiak, Marcin, Owczarek, Katarzyna, Grzanka, Dariusz, Durzynska, Julia, Pyrc, Krzysztof, Borowiak, Malgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212970/
https://www.ncbi.nlm.nih.gov/pubmed/35756892
http://dx.doi.org/10.1016/j.isci.2022.104594
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author Szlachcic, Wojciech J.
Dabrowska, Agnieszka
Milewska, Aleksandra
Ziojla, Natalia
Blaszczyk, Katarzyna
Barreto-Duran, Emilia
Sanak, Marek
Surmiak, Marcin
Owczarek, Katarzyna
Grzanka, Dariusz
Durzynska, Julia
Pyrc, Krzysztof
Borowiak, Malgorzata
author_facet Szlachcic, Wojciech J.
Dabrowska, Agnieszka
Milewska, Aleksandra
Ziojla, Natalia
Blaszczyk, Katarzyna
Barreto-Duran, Emilia
Sanak, Marek
Surmiak, Marcin
Owczarek, Katarzyna
Grzanka, Dariusz
Durzynska, Julia
Pyrc, Krzysztof
Borowiak, Malgorzata
author_sort Szlachcic, Wojciech J.
collection PubMed
description Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2, and NRP1 are expressed in precursors of insulin-producing pancreatic β-cells, rendering them permissive to SARS-CoV-2 infection. We also show that SARS-CoV-2 enters and undergoes efficient replication in human multipotent pancreatic and endocrine progenitors in vitro. Moreover, we investigated mechanisms by which SARS-CoV-2 enters pancreatic cells, and found that ACE2 mediates the entry, while NRP1 and TMPRSS2 do not. Surprisingly, we found that in pancreatic progenitors, SARS-CoV-2 enters cells via cathepsin-dependent endocytosis, which is a different route than in respiratory tract. Therefore, pancreatic spheroids might serve as a model to study candidate drugs for endocytosis-mediated viral entry inhibition and to investigate whether SARS-CoV-2 infection may affect pancreas development, possibly causing lifelong health consequences.
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spelling pubmed-92129702022-06-22 SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis Szlachcic, Wojciech J. Dabrowska, Agnieszka Milewska, Aleksandra Ziojla, Natalia Blaszczyk, Katarzyna Barreto-Duran, Emilia Sanak, Marek Surmiak, Marcin Owczarek, Katarzyna Grzanka, Dariusz Durzynska, Julia Pyrc, Krzysztof Borowiak, Malgorzata iScience Article Recent studies showed that SARS-CoV-2 can infect adult human pancreas and trigger pancreatic damage. Here, using human fetal pancreas samples and 3D differentiation of human pluripotent cells into pancreatic endocrine cells, we determined that SARS-CoV-2 receptors ACE2, TMPRSS2, and NRP1 are expressed in precursors of insulin-producing pancreatic β-cells, rendering them permissive to SARS-CoV-2 infection. We also show that SARS-CoV-2 enters and undergoes efficient replication in human multipotent pancreatic and endocrine progenitors in vitro. Moreover, we investigated mechanisms by which SARS-CoV-2 enters pancreatic cells, and found that ACE2 mediates the entry, while NRP1 and TMPRSS2 do not. Surprisingly, we found that in pancreatic progenitors, SARS-CoV-2 enters cells via cathepsin-dependent endocytosis, which is a different route than in respiratory tract. Therefore, pancreatic spheroids might serve as a model to study candidate drugs for endocytosis-mediated viral entry inhibition and to investigate whether SARS-CoV-2 infection may affect pancreas development, possibly causing lifelong health consequences. Elsevier 2022-06-16 /pmc/articles/PMC9212970/ /pubmed/35756892 http://dx.doi.org/10.1016/j.isci.2022.104594 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Szlachcic, Wojciech J.
Dabrowska, Agnieszka
Milewska, Aleksandra
Ziojla, Natalia
Blaszczyk, Katarzyna
Barreto-Duran, Emilia
Sanak, Marek
Surmiak, Marcin
Owczarek, Katarzyna
Grzanka, Dariusz
Durzynska, Julia
Pyrc, Krzysztof
Borowiak, Malgorzata
SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
title SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
title_full SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
title_fullStr SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
title_full_unstemmed SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
title_short SARS-CoV-2 infects an in vitro model of the human developing pancreas through endocytosis
title_sort sars-cov-2 infects an in vitro model of the human developing pancreas through endocytosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212970/
https://www.ncbi.nlm.nih.gov/pubmed/35756892
http://dx.doi.org/10.1016/j.isci.2022.104594
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