PMC:7252096 / 18497-21224 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7252096","sourcedb":"PMC","sourceid":"7252096","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7252096","text":"Next, using a previously unpublished scRNA-seq dataset consisting of granuloma and adjacent, uninvolved lung samples from Mtb-infected NHPs (Macaca fascicularis) collected with Seq-Well S3, we identified subsets of epithelial cells expressing ACE2 and TMPRSS2 (Figure S1 ; Table S3; STAR Methods). The majority of ACE2 + TMPRSS2 + cells were, once again, type II pneumocytes (22%) and type I pneumocytes (9.7%) and were largely enriched within granulomatous regions compared with those in adjacent uninvolved lung (Figures S1B and S1C) (p = 0.006, Fisher Exact Test). ACE2 + TMPRSS2 + type II pneumocytes expressed significantly higher amounts of antimicrobial effectors such as LCN2 compared with remaining type II pneumocytes (Figure S1D). Cells with club cell/secretory, type I pneumocyte, and ciliated cell types also contained some ACE2 + TMPRSS2 + cells, but we did not have sufficient power to detect significantly differentially expressed genes between these cells and other cells within those clusters. Altogether, we identify ACE2 + TMPRSS2 + cells in lower airways of humans and NHPs with consistent cellular phenotypes and evidence supporting a potential role for IFN-associated inflammation in upregulation of ACE2.\nFigure S1 NHP Tuberculosis Infected Lung and Granuloma, Related to Figures 1 and 2\n(A). UMAP projection of epithelial cells (1,099 cells) colored by annotated cell type, tissue source, and gating as ACE2+TMPRSS2+ cells. ACE2+TMPRSS2+ cells comprise 11% of ciliated cells, 16% of club cells, 10% type I pneumocytes, and 22% type II pneumocytes. Data generated using Seq-Well S3 (Table S3).\n(B). Number of cells (left) and % (right) ACE2+TMPRSS2+ cells by tissue source (granuloma versus uninvolved lung) and cell type. Ciliated cells and club cells were omitted from this analysis as we detected too few cells (\u003c 7 total cells) belonging to these clusters in the granulomas. Statistical significance assessed by Fisher Exact Test (Table S3).\n(C). Dot plot of top cluster defining genes for each epithelial cell type and ACE2 and TMPRSS2. Dot size represents fraction of cells expressing, and color intensity represents average log(normalized UMI + 1) among all cells in each group scaled between 0 and 1 by gene. ACE2 expression is enriched in club cells (Bimodal test, Bonferroni-corrected p \u003c 0.001), ciliated cells (p \u003c 0.005), and type I pneumocytes (p \u003c 0.001). TMPRSS2 expression is enriched in type I pneumocytes (p \u003c 0.001) and ciliated cells (p \u003c 0.001) (Table S3).\n(D). Dot plot of genes differentially expressed between ACE2+TMPRSS2+ epithelial cells versus rest (Bimodal test, Bonferroni-corrected p \u003c 0.01, log fold change \u003e 0.5). (Table S3, c = number of cells, n = number of 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