SARS-CoV-2 receptor ACE2 is an interferon-stimulated gene in human airway epithelial cells and is detected in specific cell subsets across tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) which causes the disease COVID-19. SARS-CoV-2 spike (S)-protein binds ACE2, and in concert with host proteases, principally TMPRSS2, promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues, and the factors that regulate ACE2 expression, remain unknown. Here, we leverage human and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 amongst tissue-resident cell subsets. Overall design: Samples from 8 datasets are included: single-cell RNA-Seq studies: 2 human adult donors of inferior turbinate scrapings with two replicates each. Four mouse donors of nasal epithelial cells, two stimulated with IFNA and two controls with two replicates from each animal. 13 human ileal small intestine donors. 8 human lung tissue donors with mTB infection, mTB infection and HIV, or no mTB infection. Bulk RNA-seq samples: Two human donors stimulated with three replicates of each stimulation with IFNA, IFNG, IL17A, or IL4, each at increasing doses (0, 0.1 ,0.5, 1, 2, 5, 10 ng/mL) and 12 replicates of unstimulated samples. One mouse donor of cells from the trachea with three replicates of each stimulation with IFNA, IFNB, or IFNG, each at increasing doses (0, 0.1 ,0.5, 1, 2, 5, 10 ng/mL) and 12 replicates of unstimulated samples. One human cell line stimulated with three replicates of each stimulation with IFNA, IFNG, IL17A, or IL4, each at increasing doses (0, 0.1 ,0.5, 1, 2, 5, 10 ng/mL) and 12 replicates of unstimulated samples.