LitCovid-sentences  

PMC:7417788 / 17643-27296 JSONTXT 12 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T83 0-85 Sentence denotes Identification of aging-related cell-type-specific transcriptional expression changes
T84 86-296 Sentence denotes To identify cell-subtype-specific gene signatures associated with aging, we performed an integrated comparative analysis of differentially expressed genes (DEGs) from blood immune cells in the YA and AA groups.
T85 297-421 Sentence denotes We found that blood immune cells showed heterogeneous transcriptional changes affected by aging based on the number of DEGs.
T86 422-530 Sentence denotes Strikingly, BC was the cell type most affected by aging, followed by TC and MC (Figs. 3A, S6A; Table S4A–E).
T87 531-796 Sentence denotes Specifically, we found a set of 60 genes whose expression was increased in all kinds of immune cells, indicative of general oxidative stress (e.g., DDIT4, CASP4, TSPO) and an inflammatory state (e.g., DUSP2, S100A10, COX5A, PSMB6) across cell populations (Fig. 3A).
T88 797-965 Sentence denotes Conversely, genes with decreased expression shared across all cell populations included DDX17, RBM39, and SCAF11, which are involved in RNA splicing (Fig. S6A and S6B).
T89 966-1196 Sentence denotes Consistent with our understanding of the main immune cell lineages, we found that the myeloid and lymphocyte cell lineages were characterized by unique gene expression spectra, whereas TCs showed the highest heterogeneity in DEGs.
T90 1197-1353 Sentence denotes To explore the biological implications of our data in the context of aging, we used Gene Ontology (GO) and pathway analysis for each immune cell population.
T91 1354-1515 Sentence denotes Common aging-upregulated biological pathways included TNF signaling, IL-1 signaling, the apoptotic signaling pathway, and the adaptive immune response (Fig. 3B).
T92 1516-1577 Sentence denotes We found that these pathways were especially enhanced in TCs.
T93 1578-1714 Sentence denotes In addition, aging-upregulated biological pathways in MCs were enriched for interferon-gamma (IFN-γ) signaling and cell aging (Fig. 3B).
T94 1715-1934 Sentence denotes To assess the impact of aging on circulating immune cells, we selected the top 20 genes of the 60 total genes that were upregulated in all immune cells (Fig. 3A) and calculated aging scores across all immune cell types.
T95 1935-2077 Sentence denotes We found that MCs and DCs had the highest scores, suggesting that senescent cells are most likely present in these cell populations (Fig. 3C).
T96 2078-2355 Sentence denotes Moreover, when calculating the scores of individual samples, we found that individuals in the AA group had consistently higher scores than individuals in the YA group (Fig. 3D), suggesting that aging-score assessments are suitable for studying aging-related immune dysfunction.
T97 2356-2549 Sentence denotes Figure 3 Changes in transcriptional profiles during aging. (A) UpSet Plot showing the integrated comparative analysis of upregulated DEGs in major immune cell lineages between YA and AA groups.
T98 2550-2757 Sentence denotes Upregulated DEGs: upregulated in AA, downregulated in YA group. (B) Representative GO terms and pathways enriched in upregulated DEGs based on functional enrichment analysis in major immune cell populations.
T99 2758-3083 Sentence denotes P value was derived by a hypergeometric test. (C) Distribution and comparison of the aging score in immune cell populations. (D) Distribution and comparison of the aging score in all cells of each sample. (E) UpSet plot showing the integrated comparative analysis of upregulated DEGs in CD4+ T cells between YA and AA groups.
T100 3084-3141 Sentence denotes Upregulated DEGs: upregulated in AA, downregulated in YA.
T101 3142-3306 Sentence denotes The count showing the number of DEGs. (F) Representative GO terms and pathways enriched in upregulated DEGs based on functional enrichment analysis in CD4+ T cells.
T102 3307-3468 Sentence denotes P value was derived by a hypergeometric test. (G) Venn diagram showing integrated comparative analysis of upregulated DEGs in monocytes between YA and AA groups.
T103 3469-3526 Sentence denotes Upregulated DEGs: upregulated in AA, downregulated in YA.
T104 3527-3688 Sentence denotes The count showing the number of DEGs. (H) Representative GO terms and pathways enriched in upregulated DEGs based on functional enrichment analysis in monocytes.
T105 3689-4038 Sentence denotes P value was derived by a hypergeometric test. (I) Violin plots showing the distribution of normalized expression levels of selected aging-associated genes in all DC cluster between YA and AA groups. (J) t-SNE plots segregated on the basis of DC subsets. (K) Representative GO terms and pathways enriched in biased DEGs of cDC2-A and cDC2-B clusters.
T106 4039-4195 Sentence denotes P value was derived by a hypergeometric test. (L) CLEC12A expression in cDC2 is shown as flow cytometry histogram. (M) Percentage of CLEC12A+ cells in cDC2.
T107 4196-4294 Sentence denotes P value are based on two-tailed Mann-Whitney-Wilcoxon tests between YA and AA groups (n = 3/group)
T108 4295-4418 Sentence denotes By analyzing age-associated DEGs in CD4+ TCs, we found enrichment in inflammatory and effector genes (Tables S5A and 6A–E).
T109 4419-4585 Sentence denotes To determine cell-subtype-specific gene signatures within different CD4+ TC subpopulations, we generated UpSet plots of upregulated DEGs in different CD4+ TC subsets.
T110 4586-4737 Sentence denotes We found a range of subtype-specific patterns, including the IL2 receptor (IL2RA) in Naive cells, CCR10 in Tem, and GZMB and TRBV11-2 in Tex (Fig. 3E).
T111 4738-4876 Sentence denotes GO and pathway analysis of the DEGs demonstrated that effector and memory subsets were most affected by aging based on the number of DEGs.
T112 4877-5023 Sentence denotes For example, in CD4 Tem, TNF, interleukin signaling and apoptotic pathways were enhanced, whereas mRNA processing was impaired (Figs. 3F and S6C).
T113 5024-5178 Sentence denotes Analysis of CD8+ TC status indicated that the AA group had increased expression of chemokines and granzyme family members (Fig. S6D; Tables S5B and 7A–D).
T114 5179-5473 Sentence denotes Moreover, aging was associated with a decreased proportion of CD8 Naive with increased apoptotic signaling pathway and lymphocyte activation and an expanded CD8 Tem compartment with increased cytokine production as well as reduced chromatin remodeling and antiviral function (Fig. S6E and S6F).
T115 5474-5662 Sentence denotes In addition, T-mito in aged group was associated with the upregulated inflammatory signaling molecules HLA-DRB5, PDCD5 and PSMA2 (Fig. S6G; Table S5C) and inflammatory pathways (Fig. S6H).
T116 5663-5830 Sentence denotes Analysis of NKs status revealed that the AA group had a smaller fraction of the CD56bright NK1 population and expanded late low-cytotoxic NK subsets than the YA group.
T117 5831-5993 Sentence denotes Notably, NKs in the AA group had increased expression of DDIT4, ISG20, and CASP4 and decreased expression of DDX17, PCBP1 and TRIM56 (Figs. 3A, S6A; Table S8A–C).
T118 5994-6169 Sentence denotes These genes were mostly enriched in apoptotic signaling pathways and cellular responses to lipopolysaccharide, along with decreased virus defense responses (Fig. S6I and S6J).
T119 6170-6343 Sentence denotes As for BCs, we found increased expression of JUNB, IGHA1, SSR4 and CXCR4, indicative of increased memory BC signature and activity during aging (Figs. 3A, S7A; Table S9A–D).
T120 6344-6516 Sentence denotes Moreover, the comparative functional analysis of aging-associated DEGs revealed that Naive BC in the AA group had increased cytokine-mediated signaling pathways (Fig. S7B).
T121 6517-6677 Sentence denotes Additionally, analysis of downregulated DEGs and pathways in the AA group demonstrated that BCs were associated with reduced viral defense responses (Fig. S7C).
T122 6678-6807 Sentence denotes These results indicate that NKs and BCs lose their capacity for antiviral activity with upregulated inflammatory states in aging.
T123 6808-6952 Sentence denotes We next studied aging-associated DEGs in MCs and found enrichment in inflammatory genes, such as IL1B, TNF and CXCL8, in the AA group (Fig. 3A).
T124 6953-7112 Sentence denotes All MC subsets had increased expression of the chemokines, TNF, IL1B and CDKN1A and decreased expression of SIGLEC14 and CLEC12A (Figs. 3G, S6A; Table S10A–C).
T125 7113-7483 Sentence denotes Analysis of aging-related DEGs demonstrated that the CD14 MC subset was most affected by aging, as reflected by the increased NOD-like receptor signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, inflammasome pathway, and MAPK pathway (Fig. 3H) and the obvious decrease in RNA splicing, autophagy, and vesicle-mediated transport (Fig. S7D).
T126 7484-7670 Sentence denotes To complete our DEG and GO survey of immune lineage cells and their subtypes, we next analyzed aging-associated DEGs in DCs in the YA and AA groups (Figs. 3I, S7E and S7I; Table S11A–D).
T127 7671-7856 Sentence denotes Among the upregulated DEGs, IFN-stimulated genes (IFITM2, ISG20), TNF and IL1B indicated an overactive inflammatory response in DC clusters in the AA group (Figs. 3A, 3I, S7E, and S7I).
T128 7857-7996 Sentence denotes We observed that overrepresented pathways in DCs from the AA group included apoptotic, MAPK, IL-1, and IFN-γ signaling pathways (Fig. S7F).
T129 7997-8341 Sentence denotes Notably, CLEC12A and TXNIP, which are critical for the antigen-presentation function of DCs; and MALAT1 and AHR, which are critical to inducing tolerogenic DCs (Son et al., 2008; Hutten et al., 2016; Wu et al., 2018), were decreased in AA DCs (Figs. 3I, S7G, and S7I), reflecting the decreased antigen-presenting ability of aged DCs (Fig. S7H).
T130 8342-8453 Sentence denotes These results indicate that DCs acquire an inflammatory state with age but lose the antigen-presenting ability.
T131 8454-8585 Sentence denotes Within DC clusters, we found distinct aging manifestations in the cDC2 subsets by comparing DC clusters in the t-SNE map (Fig. 3J).
T132 8586-8754 Sentence denotes Cells from the YA group grouped together in clusters 0 and 1 (named cDC2-A), whereas cells in AA group grouped distinctively in clusters 3, 4, 10 and 11 (named cDC2-B).
T133 8755-9059 Sentence denotes The expression signature of cDC2-A cells included antigen presentation-related genes such as AHR, CLEC4E, and CLEC12A, whereas the expression signature of cDC2-B cells included inflammatory and aging-associated genes such as IFN-stimulated genes, IL1B, CDKN2D, DDIT4, CXCL8, and DUSP2 (Fig. S7J and S7K).
T134 9060-9396 Sentence denotes Moreover, the comparative functional analysis of DEGs between the two clusters indicated that cDC2-A had intact immune regulation and antigen presentation function, while aging-related cDC2-B with high HLA-DQA2 expression exhibited increased inflammatory signaling pathways, such as the response to hypoxia and IL-1 signaling (Fig. 3K).
T135 9397-9487 Sentence denotes We further confirmed that CLEC12A+ cDC2s were decreased in aging by FACS (Fig. 3L and 3M).
T136 9488-9653 Sentence denotes Taken together, these findings indicate that aging curtails DC antigen presentation ability and upregulates inflammatory and aging-associated gene expression in DCs.