LitCovid-sentences  

PMC:7371427 / 37002-45812 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T218 0-64 Sentence denotes Expression of coronavirus receptors in other tissues by scRNAseq
T219 65-211 Sentence denotes We evaluated the expression profiles of ACE2, ANPEP, DPP4, and TMPRSS2 across various other human and mouse tissues by single-cell RNA-sequencing.
T220 212-619 Sentence denotes The complete set of studies profiled is outlined in Supplementary file 1 and includes both tissues which were identified from bulk RNA-sequencing as potential sites of expression for one or more receptors (e.g. kidney, adipose tissue, heart, testis, prostate, blood/immune system) as well as other tissues which did not show any evidence for expression at the bulk level (e.g. brain, retina, ovary, uterus).
T221 620-751 Sentence denotes The analysis of data from all other tissues is discussed below with corresponding images found in Figure 2—figure supplements 3–18.
T222 752-1152 Sentence denotes Our analyses of bulk RNA-seq, proteomics, and IHC demonstrated that all coronavirus receptors are highly expressed in the kidney in addition to the small intestine (Figure 2—figure supplements 2,6). scRNAseq of human and murine kidney corroborates this finding, showing that ACE2, DPP4, and ANPEP are each robustly expressed in epithelial cells of the proximal tubules (Figure 2—figure supplement 5).
T223 1153-1439 Sentence denotes Although clinical data suggests that SARS-CoV-2 does not reside in the urine (Wang et al., 2020c), we wondered whether ACE2, DPP4, and ANPEP show an overlapping pattern of expression heterogeneity among proximal tubular cells similar to that observed among small intestinal enterocytes.
T224 1440-1762 Sentence denotes To address this, we computed cosine similarity scores between gene expression vectors specifically among ~27,000 recovered human proximal tubule epithelial cells (Stewart et al., 2019) and found that again DPP4 and ANPEP are among the genes with the most similar expression profiles to ACE2 (Figure 2—figure supplement 3).
T225 1763-2044 Sentence denotes This is further supported by the strong transcriptional correlations among GTEx kidney samples (n = 85) by bulk RNA-seq, where DPP4 and ANPEP are again among the top 1% of gene correlations to ACE2 among the ~16,600 genes with mean expression >1 TPM (Figure 2—figure supplement 6).
T226 2045-2308 Sentence denotes These observations are quite consistent with our previous analysis of small intestinal data and together may suggest an underlying transcriptional network which coordinates the expression of coronavirus entry receptors across diverse human tissues and cell types.
T227 2309-2542 Sentence denotes We then examined coronavirus receptor expression in the heart given the relatively high expression of ACE2 by bulk RNA-seq and the strong literature association identified between this gene-tissue pair (Figure 2—figure supplement 7).
T228 2543-2694 Sentence denotes In the human heart, ACE2 is detected in 11% of cells or fewer from multiple populations including smooth muscle cells, cardiomyocytes, and fibroblasts.
T229 2695-2954 Sentence denotes It is detected in a higher fraction of cardiac myofibroblasts from the Tabula Muris study (Figure 2—figure supplement 7C–D) while showing no appreciable expression in any cardiac populations from the Mouse Cell Atlas dataset (Figure 2—figure supplement 7E–F).
T230 2955-3062 Sentence denotes We consider this evidence inconclusive in light of the discordant IHC patterns observed in HPA (not shown).
T231 3063-3237 Sentence denotes This disagreement both within and across data types highlights the heart as a tissue which certainly requires thorough follow-up regarding the intricacies of ACE2 expression.
T232 3238-3366 Sentence denotes Across multiple studies of adipose tissue, ACE2 is not strongly expressed in any cell population (Figure 2—figure supplement 8).
T233 3367-3658 Sentence denotes Of note, this includes studies of the murine adipose stromovascular fraction (Figure 2—figure supplement 8A–D) along with unfractionated adipose tissue subjected to single nucleus RNA-seq (sNuc-seq) which allows for the capture and sequencing of adipocytes (Figure 2—figure supplement 8E–F).
T234 3659-3768 Sentence denotes DPP4 and ANPEP are both detected in adipose stromal populations along with smaller fractions of immune cells.
T235 3769-3999 Sentence denotes Across multiple datasets, TMPRSS2 is exclusively expressed in cells defined by canonical epithelial markers (e.g. EPCAM, KRT8, CLDN3, KRT18), suggesting epithelial contamination of the adipose tissue preparations in these studies.
T236 4000-4271 Sentence denotes In the testis, ACE2 expression was unexpectedly low by scRNAseq (Figure 2—figure supplement 9A–D) given its high expression by bulk RNA-seq (Figure 2—figure supplement 2A), strong staining by IHC, and high detection levels by proteomics (Figure 2—figure supplement 2B–C).
T237 4272-4317 Sentence denotes The reason for this discrepancy is not clear.
T238 4318-4549 Sentence denotes Based on the strong protein and bulk RNA-seq evidence, we suggest that SARS-CoV-2 may indeed be able to infect certain testicular cells, but our scRNAseq analysis did not shed light on the most likely cellular targets in this case.
T239 4550-4761 Sentence denotes In both human and mouse ovary, coronavirus entry receptors and TMPRSS2 are not appreciably expressed, which is consistent with a lack of detection by our other data modalities (Figure 2—figure supplement 10A–D).
T240 4762-4912 Sentence denotes In the liver, expression of these genes was generally consistent with the protein expression patterns observed by IHC (Figure 2—figure supplement 11).
T241 4913-5074 Sentence denotes ACE2 shows minimal detection throughout liver populations, while both DPP4 and ANPEP are expressed in the epithelial compartment (Figure 2—figure supplement 12).
T242 5075-5187 Sentence denotes ANPEP expression is particularly high in the EPCAM+ population of cells which may mark hepatic progenitor cells.
T243 5188-5374 Sentence denotes TMPRSS2 is also expressed in these cells and in a subset of mature hepatocytes, which is discordant with the lack of TMPRSS2 staining in the liver by IHC (Figure 2—figure supplement 12).
T244 5375-5506 Sentence denotes In the pancreas, ACE2 is expressed in different cell types including acinar cells and ductal cells (Figure 2—figure supplement 12).
T245 5507-5737 Sentence denotes DPP4 is robustly expressed in pancreatic alpha cells with lower expression detected in ~20% of ductal cells, while TMPRSS2 and ANPEP are both strongly expressed in the acinar and ductal populations (Figure 2—figure supplement 12).
T246 5738-5859 Sentence denotes These patterns are largely consistent with our observations of protein expression by IHC (Figure 2—figure supplement 11).
T247 5860-6018 Sentence denotes To assess expression in blood and immune organs, we analyzed scRNAseq studies from blood, spleen, bone marrow, and thymus (Figure 2—figure supplements 13–14).
T248 6019-6109 Sentence denotes Generally ACE2 and TMPRSS2 are not highly expressed in any populations from these tissues.
T249 6110-6336 Sentence denotes DPP4 is expressed in subsets of T cells across these studies (Figure 2—figure supplement 14) along with B cells and various progenitor populations in the bone marrow from the Tabula Muris study (Figure 2—figure supplement 14).
T250 6337-6497 Sentence denotes ANPEP expression was mostly restricted to monocytes and macrophages along with some small bone marrow progenitor populations (Figure 2—figure supplement 14B,D).
T251 6498-6657 Sentence denotes Similarly, ANPEP expression in monocytes and macrophages may provide an alternative non-epithelial route of infection for other coronaviruses such as CoV-229E.
T252 6658-6816 Sentence denotes In both bladder and prostate samples from human and mouse, TMPRSS2 is robustly expressed in various epithelial populations (Figure 2—figure supplement 15A–H).
T253 6817-7088 Sentence denotes The coronavirus entry receptors are only minimally detected across all bladder cell populations (Figure 2—figure supplement 15A–F), whereas DPP4 and ANPEP are detected in subsets of human prostate luminal cells (~8% of 18%, respectively) (Figure 2—figure supplement 15H).
T254 7089-7196 Sentence denotes ACE2 expression is low across all recovered populations from the prostate (Figure 2—figure supplement 15H).
T255 7197-7390 Sentence denotes In the mouse uterus dataset of ~3700 cells from the Mouse Cell Atlas (Figure 2—figure supplement 16A), Ace2 was uniformly absent from all recovered populations (Figure 2—figure supplement 16B).
T256 7391-7543 Sentence denotes Anpep is robustly detected in ~60% of glandular epithelial cells along with a smaller fraction (~10%) of stromal cells (Figure 2—figure supplement 16B).
T257 7544-7778 Sentence denotes Dpp4 expression is detected in ~17% of dendritic cells (n = 23 of 131) along with ~5% of glandular epithelial cells, and Tmprss2 is expressed in a similarly small fraction of the epithelial population (Figure 2—figure supplement 16B).
T258 7779-8168 Sentence denotes Finally, we assessed the expression of these genes in central nervous system (CNS) tissues despite their uniformly low expression and lack of detection in brain samples from GTEx and HPA, respectively (data not shown). scRNAseq data suggests similarly low expression across CNS populations, including various regions of the mouse brain and the human retina (Figure 2—figure supplement 17).
T259 8169-8339 Sentence denotes From the Tabula Muris study, Ace2 is detected in a small number of pericytes (22 of 146) and an even lower fraction of endothelial cells (Figure 2—figure supplement 17B).
T260 8340-8575 Sentence denotes Dpp4 is also expressed here in ~20% of endothelial cells (Figure 2—figure supplement 17B), which may warrant follow-up but importantly is not reflected in endothelial cells of the cerebral cortex by IHC (Figure 2—figure supplement 18).
T261 8576-8810 Sentence denotes In all brain-derived cell populations from the Mouse Cell Atlas (Figure 2—figure supplement 17C–D) and human retina-derived populations (Figure 2—figure supplement 17E–F), these genes were uniformly not detected at significant levels.