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

We next sought to identify differentially expressed genes (DEGs) in AT2 cells based on ACE2 expression. A cutoff of absolute gene expression fold-change >1.2 and an FDR q-value < 0.05 were applied to select DEGs between ACE2-expressing and ACE2-absent AT2 cells. We found genes upregulated in ACE2-expressing AT2 cells that are highly pertinent to lung epithelial biology and disease such as HHIP (lung branching and chronic obstructive pulmonary disease/COPD, 31, 32 ) , FGG (fibrosis, pneumonia and inflammation, 33, 34 ) and C4BPA (complement system, pneumonia and infection, 35, 36 ) ( Fig. 3) . In addition, we found that ACE2-expressing AT2 cells exhibited significantly higher expression of scavengers such as CD36 37 and DMBT1, a pattern recognition receptor that plays crucial host defense roles against bacterial and viral pathogens including influenza A and human immune deficiency virus I (HIV-I) 38 . Interestingly, DMBT1 expression was markedly and distinctly highest in AT2 cells relative to other lung cell subsets (Fig. S5a) . Also, DMBT1 expression in AT2 cells was higher compared to other coronavirus receptors such as the MERS-CoV receptor DPP4 39, 40 and BSG (also known as CD147) which was recently suggested to represent a potential alternate route of entry for SARS-CoV-2 41 (Fig. S5a) . Also, DMBT1 displayed similar patterns of expression with ACE2 among AT2 (Fig. S5b ) and lung malignant cell (Fig. S5c) subclusters.