tetano
Editor, Senior Moderator
Stem Cell Reports
. 2021 Apr 13;16(4):940-953.
doi: 10.1016/j.stemcr.2021.02.019.
Human Pluripotent Stem Cell-Derived Intestinal Organoids Model SARS-CoV-2 Infection Revealing a Common Epithelial Inflammatory Response
Aditya Mithal[SUP] 1 [/SUP], Adam J Hume[SUP] 2 [/SUP], Jonathan Lindstrom-Vautrin[SUP] 3 [/SUP], Carlos Villacorta-Martin[SUP] 3 [/SUP], Judith Olejnik[SUP] 2 [/SUP], Esther Bullitt[SUP] 4 [/SUP], Anne Hinds[SUP] 5 [/SUP], Elke M?hlberger[SUP] 6 [/SUP], Gustavo Mostoslavsky[SUP] 7 [/SUP]
Affiliations
Abstract
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.
Keywords: SARS-CoV-2; extrapulmonary COVID-19; host response; human induced pluripotent stem cells; intestinal and colonic organoids; intestinal epithelial cells.
. 2021 Apr 13;16(4):940-953.
doi: 10.1016/j.stemcr.2021.02.019.
Human Pluripotent Stem Cell-Derived Intestinal Organoids Model SARS-CoV-2 Infection Revealing a Common Epithelial Inflammatory Response
Aditya Mithal[SUP] 1 [/SUP], Adam J Hume[SUP] 2 [/SUP], Jonathan Lindstrom-Vautrin[SUP] 3 [/SUP], Carlos Villacorta-Martin[SUP] 3 [/SUP], Judith Olejnik[SUP] 2 [/SUP], Esther Bullitt[SUP] 4 [/SUP], Anne Hinds[SUP] 5 [/SUP], Elke M?hlberger[SUP] 6 [/SUP], Gustavo Mostoslavsky[SUP] 7 [/SUP]
Affiliations
- PMID: 33852884
- PMCID: PMC8042780
- DOI: 10.1016/j.stemcr.2021.02.019
Abstract
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.
Keywords: SARS-CoV-2; extrapulmonary COVID-19; host response; human induced pluripotent stem cells; intestinal and colonic organoids; intestinal epithelial cells.