Single-cell analysis of human lung epithelia reveals concomitant expression of the SARS-CoV-2 receptor ACE2 with multiple virus receptors and scavengers in alveolar type II cells

Guangchun Han; Ansam Sinjab; Warapen Treekitkarnmongkol; Patrick Brennan; Kieko Hara; Kyle Chang; Elena Bogatenkova; Beatriz Sanchez-Espiridion; Carmen Behrens; Boning Gao; Luc Girard; Jianjun Zhang; Boris Sepesi; Tina Cascone; Lauren Byers; Don L. Gibbons; Jichao Chen; Seyed Javad Moghaddam; Edwin J. Ostrin; Junya Fujimoto; Jerry Shay; John V. Heymach; John D. Minna; Steven Dubinett; Paul A. Scheet; Ignacio I. Wistuba; Edward Hill; Shannon Telesco; Christopher Stevenson; Avrum E. Spira; Linghua Wang; Humam Kadara

Motivated by the current and unprecedented global health crisis, we leveraged our ongoing lung single-cell RNA-sequencing (scRNA-seq) efforts to interrogate the expression of the SARS-CoV-2 receptor ACE2 in a unique cohort of 70,085 lung epithelial cells from tumor and matched uninvolved normal lung tissues from five lung adenocarcinoma (LUAD) patients. Among all lung epithelial subsets, we found that ACE2 expression was higher in uninvolved AT2 cells and malignant epithelial cells. We interrogated single-cell gene co-expression profiles and found that ACE2-epressing AT2 cells concurrently expressed other genes with important yet understudied roles in lung pathobiology including fibrosis, modulation of chronic inflammation and innate host-defense mechanisms by additional viral receptors and scavengers, particularly among cells from smokers. Our single-cell analyses highlight additional possible receptors that may play a role in SARS-CoV-2 infection in the lung epithelium and, thus, are plausible targets that can be repurposed for clinical management of COVID-19.