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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

LitCovid-PD-MONDO

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

{"project":"LitCovid-PD-GO-BP","denotations":[{"id":"T36447","span":{"begin":277,"end":291},"obj":"http://purl.obolibrary.org/obo/GO_0019076"},{"id":"T91940","span":{"begin":3786,"end":3805},"obj":"http://purl.obolibrary.org/obo/GO_0008152"},{"id":"T24720","span":{"begin":4035,"end":4050},"obj":"http://purl.obolibrary.org/obo/GO_0016032"}],"text":"Ileal Absorptive Enterocytes Express Host Factors Used by SARS-CoV-2\nNext, we examined several other tissues for ACE2-expressing cells on the basis of the location of hallmark symptoms of COVID-19, focusing on the gastrointestinal tract due to reports of clinical symptoms and viral shedding (Xiao et al., 2020). Leveraging a previously unpublished scRNA-seq atlas of NHP (M. mulatta) tissues collected with Seq-Well v1, we observed that the majority of ACE2 + cells reside in the small intestine, principally within the ileum, jejunum, and, to a lesser extent, the liver and colon (Figure 3 A; STAR Methods). Critically, we note that, in this experiment, the dissociation method used on each tissue was optimized to preserve immune cell recovery, and therefore under-sampled stromal and epithelial populations, as well as neurons from the brain. Within the ileum, we identified ACE2 + cells as absorptive enterocytes on the basis of specific expression of ACE2 within cells defined by APOA1, SI, FABP6, and ENPEP, among others, by a likelihood-ratio test (Figures 3B and 3C) (p \u003c 1E−300, 62% of all absorptive enterocytes; see Table S4). All other epithelial subtypes expressed ACE2 to a lesser extent, and variably co-expressed ACE2 with TMPRSS2 (see Table S4 for full statistics).\nFigure 3 NHP and Human Ileal Absorptive Enterocytes Co-Express ACE2 and TMPRSS2\n(A) Expression ACE2 across diverse tissues in healthy NHPs (n = 3 animals; 52,858 cells).\n(B) Schematic of protocol for isolation of NHP ileum (n = 5) at necropsy for scRNA-seq using Seq-Well v1, and computational pipeline to identify cell types by using unbiased methods. Shown on the right is a UMAP projection of 4,515 cells colored by cell type.\n(C) Dot plot of 2 defining genes for each cell type, with ACE2 and TMPRSS2. Dot size represents fraction of cells within cell type expressing a given gene, and color intensity represents binned count-based expression amounts (log(scaled UMI+1)) among expressing cells. All cluster defining genes are provided in Table S4. Red arrow indicates cell type with largest proportion of ACE2+TMPRSS2+ cells.\n(D) Schematic of protocol for isolation of human ileal cells from endoscopic pinch biopsies in non-inflamed regions (n = 13). Shown on the right is a tSNE plot of 13,689 epithelial cells selected from original dataset generated by 10x 3′ v2 (see Figure S2), colored by cellular subsets.\n(E). Dot plot of 2 defining genes for each cell type, with ACE2 and TMPRSS2. Dot size represents fraction of cells within cell type expressing a given gene, and color intensity represents binned count-based expression amounts (log(scaled UMI+1)) among expressing cells. All cluster defining genes are provided in Table S5. Red arrow indicates cell type with largest proportion of ACE2+TMPRSS2+ cells.\n(F). Expression of ACE2 (left) and TMPRSS2 (right) among all epithelial subsets from human donors.\nSee also Figure S2 and Tables S4 and S5.\nPersistent 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 cells)."}

LitCovid-sentences

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T11","span":{"begin":4196,"end":4212},"obj":"Phenotype"}],"attributes":[{"id":"A11","pred":"hp_id","subj":"T11","obj":"http://purl.obolibrary.org/obo/HP_0002721"}],"text":"Ileal Absorptive Enterocytes Express Host Factors Used by SARS-CoV-2\nNext, we examined several other tissues for ACE2-expressing cells on the basis of the location of hallmark symptoms of COVID-19, focusing on the gastrointestinal tract due to reports of clinical symptoms and viral shedding (Xiao et al., 2020). Leveraging a previously unpublished scRNA-seq atlas of NHP (M. mulatta) tissues collected with Seq-Well v1, we observed that the majority of ACE2 + cells reside in the small intestine, principally within the ileum, jejunum, and, to a lesser extent, the liver and colon (Figure 3 A; STAR Methods). Critically, we note that, in this experiment, the dissociation method used on each tissue was optimized to preserve immune cell recovery, and therefore under-sampled stromal and epithelial populations, as well as neurons from the brain. Within the ileum, we identified ACE2 + cells as absorptive enterocytes on the basis of specific expression of ACE2 within cells defined by APOA1, SI, FABP6, and ENPEP, among others, by a likelihood-ratio test (Figures 3B and 3C) (p \u003c 1E−300, 62% of all absorptive enterocytes; see Table S4). All other epithelial subtypes expressed ACE2 to a lesser extent, and variably co-expressed ACE2 with TMPRSS2 (see Table S4 for full statistics).\nFigure 3 NHP and Human Ileal Absorptive Enterocytes Co-Express ACE2 and TMPRSS2\n(A) Expression ACE2 across diverse tissues in healthy NHPs (n = 3 animals; 52,858 cells).\n(B) Schematic of protocol for isolation of NHP ileum (n = 5) at necropsy for scRNA-seq using Seq-Well v1, and computational pipeline to identify cell types by using unbiased methods. Shown on the right is a UMAP projection of 4,515 cells colored by cell type.\n(C) Dot plot of 2 defining genes for each cell type, with ACE2 and TMPRSS2. Dot size represents fraction of cells within cell type expressing a given gene, and color intensity represents binned count-based expression amounts (log(scaled UMI+1)) among expressing cells. All cluster defining genes are provided in Table S4. Red arrow indicates cell type with largest proportion of ACE2+TMPRSS2+ cells.\n(D) Schematic of protocol for isolation of human ileal cells from endoscopic pinch biopsies in non-inflamed regions (n = 13). Shown on the right is a tSNE plot of 13,689 epithelial cells selected from original dataset generated by 10x 3′ v2 (see Figure S2), colored by cellular subsets.\n(E). Dot plot of 2 defining genes for each cell type, with ACE2 and TMPRSS2. Dot size represents fraction of cells within cell type expressing a given gene, and color intensity represents binned count-based expression amounts (log(scaled UMI+1)) among expressing cells. All cluster defining genes are provided in Table S5. Red arrow indicates cell type with largest proportion of ACE2+TMPRSS2+ cells.\n(F). Expression of ACE2 (left) and TMPRSS2 (right) among all epithelial subsets from human donors.\nSee also Figure S2 and Tables S4 and S5.\nPersistent 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 cells)."}

LitCovid-PubTator

2_test

{"project":"2_test","denotations":[{"id":"32413319-32284613-20790466","span":{"begin":3074,"end":3078},"obj":"32284613"},{"id":"32413319-30361514-20790467","span":{"begin":4352,"end":4356},"obj":"30361514"},{"id":"32413319-27941242-20790468","span":{"begin":4650,"end":4654},"obj":"27941242"},{"id":"32413319-27500281-20790469","span":{"begin":4672,"end":4676},"obj":"27500281"}],"text":"Ileal Absorptive Enterocytes Express Host Factors Used by SARS-CoV-2\nNext, we examined several other tissues for ACE2-expressing cells on the basis of the location of hallmark symptoms of COVID-19, focusing on the gastrointestinal tract due to reports of clinical symptoms and viral shedding (Xiao et al., 2020). Leveraging a previously unpublished scRNA-seq atlas of NHP (M. mulatta) tissues collected with Seq-Well v1, we observed that the majority of ACE2 + cells reside in the small intestine, principally within the ileum, jejunum, and, to a lesser extent, the liver and colon (Figure 3 A; STAR Methods). Critically, we note that, in this experiment, the dissociation method used on each tissue was optimized to preserve immune cell recovery, and therefore under-sampled stromal and epithelial populations, as well as neurons from the brain. Within the ileum, we identified ACE2 + cells as absorptive enterocytes on the basis of specific expression of ACE2 within cells defined by APOA1, SI, FABP6, and ENPEP, among others, by a likelihood-ratio test (Figures 3B and 3C) (p \u003c 1E−300, 62% of all absorptive enterocytes; see Table S4). All other epithelial subtypes expressed ACE2 to a lesser extent, and variably co-expressed ACE2 with TMPRSS2 (see Table S4 for full statistics).\nFigure 3 NHP and Human Ileal Absorptive Enterocytes Co-Express ACE2 and TMPRSS2\n(A) Expression ACE2 across diverse tissues in healthy NHPs (n = 3 animals; 52,858 cells).\n(B) Schematic of protocol for isolation of NHP ileum (n = 5) at necropsy for scRNA-seq using Seq-Well v1, and computational pipeline to identify cell types by using unbiased methods. Shown on the right is a UMAP projection of 4,515 cells colored by cell type.\n(C) Dot plot of 2 defining genes for each cell type, with ACE2 and TMPRSS2. Dot size represents fraction of cells within cell type expressing a given gene, and color intensity represents binned count-based expression amounts (log(scaled UMI+1)) among expressing cells. All cluster defining genes are provided in Table S4. Red arrow indicates cell type with largest proportion of ACE2+TMPRSS2+ cells.\n(D) Schematic of protocol for isolation of human ileal cells from endoscopic pinch biopsies in non-inflamed regions (n = 13). Shown on the right is a tSNE plot of 13,689 epithelial cells selected from original dataset generated by 10x 3′ v2 (see Figure S2), colored by cellular subsets.\n(E). Dot plot of 2 defining genes for each cell type, with ACE2 and TMPRSS2. Dot size represents fraction of cells within cell type expressing a given gene, and color intensity represents binned count-based expression amounts (log(scaled UMI+1)) among expressing cells. All cluster defining genes are provided in Table S5. Red arrow indicates cell type with largest proportion of ACE2+TMPRSS2+ cells.\n(F). Expression of ACE2 (left) and TMPRSS2 (right) among all epithelial subsets from human donors.\nSee also Figure S2 and Tables S4 and S5.\nPersistent 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 cells)."}

PMC:7252096 / 21226-26785 JSONTXT

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PMC:7252096 / 21226-26785 JSON TXT