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

Our findings on the significant associations between ACE2 and DMBT1 prompted us to probe the correlation of both genes in the AT2 compartment. We performed pseudo-bulk analysis of the AT2 cluster (by sample) in our cohort and found that DMBT1 and ACE2 exhibited positive correlation (R = 0.3) albeit not reaching statistical significance (Fig. 5a) . To validate this finding in larger cohorts, we performed deconvolution analysis of bulk RNA-seq data of the cancer genome atlas (TCGA) LUAD cohort to estimate the abundance of AT2 cells in normal lung tissues (n = 110). Both DMBT1 and ACE2 expression levels significantly and positively correlated with AT2 fractions (indicated by the AT2 meta-score, P < 0.05) (Fig. 5b) . Interestingly, BSG, the other recently proposed entry point for SARS-CoV-2, also significantly and positively correlated with the AT2 meta-score in the normal lung tissues (P < 0.05) (Fig. 5b) . Similar results were obtained with TMPRSS2 (P < 0.05) but not ADAM17 (Fig. S6a) . Further, among TCGA normal lung tissues with high AT2 fractions (meta-score > 15.47), DMBT1 expression significantly and positively correlated with ACE2 (R = 0.41, P < 0.05) (Fig. 5c) .