Fig. 2 |. An integrated oral cell atlas reveals broad epithelial infection susceptibilities.

a, To characterize the vulnerabilities of oral tissues to infection by SARS-CoV-2 and other common viruses, we integrated unpublished data from human oral gingiva and minor SGs. b, These 50 populations were jointly annotated before integration into 34 cell clusters to create the first human pan-oral cell atlas (see gene signatures in Extended Data Fig. 2a and Supplementary Table 2). These results illustrate that both shared and unique cell populations are represented in the gingiva and SG. c, Vulnerabilities to infection by coronaviruses, influenza and rhinovirus C can be predicted based on entry factor expression and visualized using expression matrices. Epithelia appear especially at risk for viral infection. d, When focused on the nine epithelial cell populations, vulnerabilities to SARS-CoV-2 were apparent in both SG and mucosa. These results strongly suggest that the oral cavity might be vulnerable to viral infection, especially for SARS-CoV-2. Expression matrices, including a low-frequency ACE2/TMPRSS2 co-expressing cells in Basal 1, ducts, mucous acini and myoepithelial clusters, further supporting SARS-CoV-2 infection susceptibilities. e, UMAPs demonstrate distinct cluster vulnerabilities, with ACE2 highest in most oral epithelia; however, expression of proteases demonstrated tissue-specific expression patterns with TMPRSS2 (enriched for SGs) and TMPRSS11D (enriched for mucosal cells). Endosomal proteases, CTSB and CTSL exhibited broad expression across vulnerable cell types. f, Normalized expression of epithelial clusters across oral, nasal and intestinal tissues demonstrate the relatively equivalent expression level of oral sites, especially in the minor SG. NK, natural killer; DC, dendritic cell; TA, transit amplifying.