Human Pluripotent Stem Cell-Derived Intestinal Organoids Model SARS-CoV-2 Infection Revealing a Common Epithelial Inflammatory Response.
SARS-CoV-2
extrapulmonary COVID-19
host response
human induced pluripotent stem cells
intestinal and colonic organoids
intestinal epithelial cells
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
13 04 2021
13 04 2021
Historique:
received:
29
12
2020
revised:
23
02
2021
accepted:
24
02
2021
entrez:
14
4
2021
pubmed:
15
4
2021
medline:
27
4
2021
Statut:
ppublish
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) usually results in respiratory disease, but extrapulmonary manifestations are of major clinical interest. Intestinal symptoms of COVID-19 are present in a significant number of patients, and include nausea, diarrhea, and viral RNA shedding in feces. Human induced pluripotent stem cell-derived intestinal organoids (HIOs) represent an inexhaustible cellular resource that could serve as a valuable tool to study SARS-CoV-2 as well as other enteric viruses that infect the intestinal epithelium. Here, we report that SARS-CoV-2 productively infects both proximally and distally patterned HIOs, leading to the release of infectious viral particles while stimulating a robust transcriptomic response, including a significant upregulation of interferon-related genes that appeared to be conserved across multiple epithelial cell types. These findings illuminate a potential inflammatory epithelial-specific signature that may contribute to both the multisystemic nature of COVID-19 as well as its highly variable clinical presentation.
Identifiants
pubmed: 33852884
pii: S2213-6711(21)00099-0
doi: 10.1016/j.stemcr.2021.02.019
pmc: PMC8042780
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
940-953Subventions
Organisme : NIAID NIH HHS
ID : UC7 AI095321
Pays : United States
Organisme : NIH HHS
ID : N0175N92020C00005
Pays : United States
Organisme : NIH HHS
ID : 1R01DA051889-01
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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