Human airway lineages derived from pluripotent stem cells reveal the epithelial responses to SARS-CoV-2 infection
Ruobing Wang, Adam J. Hume, Mary Lou Beermann, Chantelle Simone-Roach, Jonathan Lindstrom-Vautrin, Jake Le Suer, Jessie Huang, Judith Olejnik, Carlos Villacorta-Martín, Esther Bullitt, Anne Hinds, Mahboobe Ghaedi, S.D. Rollins, Rhiannon B. Werder, Kristine M. Abo, Andrew A. Wilson, Elke Mühlberger, Darrell N. Kotton, Finn Hawkins
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 angiotensin-converting enzyme 2 ( ACE2), and transmembrane protease serine 2 ( TMPRSS2). Multiciliated cells are the primary initial target of SARS-CoV-2 infection. On infection with SARS-CoV-2, iPSC-airway cells generate robust interferon and inflammatory responses, and treatment with remdesivir or camostat mesylate 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.