Published on Wed Jul 07 2021

Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection

Wang, R., Hume, A., Beermann, M. L., Simone-Roach, C., Lindstrom-Vautrin, J., Le Suer, J., Huang, J., Olejnik, J., Villacorta-Martin, C., Bullitt, E., Hinds, A., Ghaedi, M., Werder, R., Abo, K., Wilson, A., Muhlberger, E., Kotton, D. N., Hawkins, F. J.

There 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

3
1
3
Abstract

There 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.