PMC:7252096 / 24168-26785 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7252096","sourcedb":"PMC","sourceid":"7252096","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7252096","text":"Persistent viral RNA in rectal swabs has been detected in pediatric infection, even after negative nasopharyngeal tests (Xu et al., 2020). In an additional dataset consisting of endoscopic biopsies from the terminal ileum of a human pediatric cohort (n = 13 donors, ranging in age from 10 to 18 years old), collected with 10X 3′ v2, we confirmed a large abundance of ACE2 + cells with selective expression within absorptive enterocytes (29.7% ACE2 +, FDR-adjusted p = 2.46E−100) (Figures 3D and 3E; Table S5; STAR Methods). Furthermore, we identified a subset (888 cells, ∼6.5% of all epithelial cells) that co-express both genes (Figures S2 A–S2C). We performed differential expression testing and GO-term enrichment using these cells relative to matched non-expressers to highlight putative biological functions enriched within them, such as metabolic processes and catalytic activity, and to identify shared phenotypes of ACE2 + TMPRSS2 + ileal cells across both human and NHP cohorts (Table S5). We speculate that viral targeting of these cells, taken from patients without overt clinical viral infection, might help explain intestinal symptoms. Finally, we compared ileal absorptive enterocytes from healthy NHPs and NHPs infected with simian-human immunodeficiency virus (SHIV) and then treated for 6 months with anti-retroviral therapy (animal and infection characteristics published in Colonna et al., 2018) (STAR Methods). We found significant upregulation of ACE2, STAT1, and IFI6 within the absorptive enterocytes of SHIV-infected animals (which maintain chronically elevated amounts of IFNs and ISGs) compared with those of uninfected controls (FDR-adjusted p \u003c 2E-7) (Figure S2D) (Deeks et al., 2017, Utay and Douek, 2016).\nFigure S2 Human and NHP Ileum, Related to Figure 3\n(A). Top: tSNE projection of all cells from healthy pediatric human ileum within a previously-unpublished 10x 3′ v2 dataset (115,569 cells). Black: higher expression of ACE2 (left), TMPRSS2 (right). Bottom: Corresponding violin plots of expression values for ACE2 (left) and TMPRSS2 (right). Solid line: epithelial cells.\n(B). Co-expression of ACE2 and TMPRSS2 by epithelial cell subset. Number indicates % of ACE2+TMPRSS2+ cells by cell subset.\n(C). tSNE projection of 13,689 cells as in Figure 3D, cells colored by co-expression of ACE2 and TMPRSS2 (black).\n(D). Expression of ACE2 and canonical interferon-responsive genes among absorptive enterocytes from Healthy (n = 2) and SHIV-infected, anti-retroviral treated animals (n = 3). Bonferroni-adjusted p-values by Wilcoxon test (healthy: 510 cells, SHIV-infected: 636 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