| Autor: |
Ruobing Wang, Adam J. Hume, Mary Lou Beermann, Chantelle Simone-Roach, Jonathan Lindstrom-Vautrin, Jake Le Suer, Jessie Huang, Judith Olejnik, Carlos Villacorta-Martin, Esther Bullitt, Anne Hinds, Mahboobe Ghaedi, Rhiannon B. Werder, Kristine M. Abo, Andrew A. Wilson, Elke Mühlberger, Darrell N. Kotton, Finn J. Hawkins |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.1101/2021.07.06.451340 |
| Popis: |
SummaryThere is an urgent need to understand how SARS-CoV-2 infects the airway epithelium and in a subset of individuals leads to severe illness or death. Induced pluripotent stem cells (iPSCs) provide a near limitless supply of human cells that can be differentiated into cell types of interest, including airway epithelium, for disease modeling. We present a human iPSC-derived airway epithelial platform, composed of the major airway epithelial cell types, that is permissive to SARS-CoV-2 infection. Subsets of iPSC-airway cells express the SARS-CoV-2 entry factors ACE2 and TMPRSS2. Multiciliated cells are the primary initial target of SARS-CoV-2 infection. Upon infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses and treatment with remdesivir or camostat methylate causes a decrease in viral propagation and entry, respectively. In conclusion, iPSC-derived airway cells provide a physiologically relevant in vitro model system to interrogate the pathogenesis of, and develop treatment strategies for, COVID-19 pneumonia.Highlights and eTOC blurbSubsets of human iPSC-airway epithelial cells express SARS-Co-V entry factors ACE2 and TMPRSS2.iPSC-airway cells are permissive to SARS-CoV-2 infection via multiciliated cells.SARS-CoV-2 infection of iPSC-airway leads to a robust interferon and inflammatory response.iPSC-airway is a physiologically relevant model to study SARS-CoV-2 infection. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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