Next, using a publicly available resource (interferome.org) that hosts genomic and transcriptomic data from cells or tissues treated with IFN, we queried ACE2 expression within human and mouse cells, searching for datasets with a log2-fold-change of >1 or < −1 compared with untreated samples, including all IFN types (Rusinova et al., 2013). We recovered 21 datasets spanning 8 distinct primary tissues or cell lines with non-trivial changes in ACE2 expression after both type I and type II IFN treatment (Figure S4 A). We observed substantial upregulation of ACE2 in primary skin and primary bronchial cells treated with either type I or type II IFN (> 5-fold upregulation compared with that in untreated cells), in strong support of our in vitro data (Figures 5C, 5D, 5G–5L, and S3D–S3F). Immune cell types, such as CD4 T cells and macrophages, were noticeably absent from datasets with a significant change in ACE2 expression after IFN stimulation or were even found to downregulate ACE2 (e.g., primary CD4 T cells + type I IFN) (Figure S4A, and in our analysis of scRNA-seq peripheral blood mononuclear cell data from Butler et al., (2018); data not shown).
Figure S4 Published Studies of Epithelial Cells Following Interferon Treatment Related to Figure 5
(A). Fold change of ACE2 expression among human or mouse datasets following Type I or Type II interferon treatment compared to untreated control. Generated from publicly available microarray data curated at interferome.org. Includes all studies with abs(fold-change) > 1.
(B). Location of transcription factors binding regions spanning −1500 bp to +500 bp from the transcription start site of ACE2 (human, top) or Ace2 (mouse, bottom). Generated from TRANSFAC data using the interferome.org database (Matys et al., 2003, Rusinova et al., 2013).