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

Recently, expansion of ACE2-expressing lung epithelia in response to cigarette smoke has also been proposed 42 and smoking was shown to activate the RAS 43 . We were thus enticed to compare the identified ACE2-co-expressed genes, along with members of the RAS, in lung epithelial cells based . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.04.16.045617 doi: bioRxiv preprint on patient smoking status. We identified genes differentially expressed between AT2 cells derived from smokers (at least 20 pack year smoking history, n = 10,901 cells) and those from non-or lightsmokers (less than five pack years, n = 16,334 cells) based on a q-value threshold of 0.05 and a foldchange cut-off of 1.5 (Fig. 4a) . While ACE2 itself was not modulated by smoking status, we found that the virus receptor and scavenger DMBT1, as well as FGG and C4BPA, were significantly increased in smoker compared to non/light smoker AT2 cells (Fig. 4a-b) . DMBT1 was not significantly differentially modulated among malignant cells based on smoking status (Fig. 4c) , though we found increased expression of BSG and members of the RAS (mostly kallikreins) in smoker (n = 9,047) compared to non/light smoker (n = 1,657) malignant cells (Fig. 4c-d) .