Single cell transcriptomes of replicatively cellular senescenct cells and ionizing radiation induced senescent cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE119807 | GEO | 2018/11/19
REPOSITORIES: GEO
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Project description:Microarrays analysis identifies WNT16in senescent fibroblasts. To identify genes expressed in replicative senescence, microarray experiments were conducted in which we compared the RNA expression profile of young MRC5 fibroblasts at population doubling 28 (PDL28) and replicative senescent MRC5 fibroblasts at PDL63. In total, 177 gene probes were upregulated and 338 gene probes were downregulated in senescent versus young MRC5 fibroblasts. Genes were classified based on mapping to KEGG pathways. Upregulated genes were enriched in three KEGG pathways, the Wingless-type MMTV integration site (WNT) signaling pathway (WNT16, PLCB4, CCND2, SFRP1, WNT5B, RAC2), cytokine-cytokine receptor interaction (TNFRSF10D, TNFRSF10B, TNFRSF10C, IL1R2, IL18, VEGFC), and the p53 signaling pathway (CDKN1A, TNFRSF10B, PERP, STEAP3, ZMAT3). Repressed genes were enriched in three KEGG pathways, cell cycle (PKMYT1, CDC7, CCNE2, MCM4, BUB1, CDC25A, CDKN1B, MCM6, PLK1, CDKN2C, CCNB2, MCM3, BUB1B, CCNA2, CDC2), cytokine-cytokine receptor interaction (KITLG, IL11, TNFSF4, CCL2, PDGFRA, TNFRSF11B, TGFBR1, IL1R1, TNFRSF19), and DNA replication (POLE, RFC2, MCM4, RNASEH2B, POLA1, DNA2, MCM6, PRIM1, RFC4, MCM3). Along with p53 transcriptional targets (CDKN1A, PERP, WIG1), genes encoding secreted factors (WNT16, MMP10, MMP3) were among the most strongly increased in senescent cells. Six arrays were hybridized with complex probes consisting of RNA isolated from MRC5 fibroblasts at population doubling 63 (undergoing replicative senescence) and RNA isolated from MRC5 fibroblats at population doubling 28 (young). The six arrays correspond to three biological replicates, each with a dye-swap technical replicate.
2010-05-18 | E-GEOD-15919 | biostudies-arrayexpress
Project description:<p><strong>BACKGROUND:</strong> Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for cell-based regenerative medicine in dentistry. PDLSCs inevitably acquire a senescent phenotype after prolonged in vitro expansion, and the key regulators of cells during replicative senescence remain unclear.</p><p><strong>METHODS:</strong> We cultured periodontal ligament stem cells to passages 4, 10 and 20 (P4, P10, P20). The senescent phenotypes, proliferation and migration ability of PDLSCs (P4, P10, P20) were detected, and non-targeted metabonomic sequencing was performed. We treated PDLSCs with AICAR and detected the expression of FOXO1, FOXO3a, FOXO6 and AMPK phosphorylation (p-AMPK) levels of replicating senescent PDLSCs to explore the correlation between the metabolic changes and the AMPK pathway.</p><p><strong>RESULTS:</strong> Immunofluorescence staining of γ-H2AX, β-galactosidase staining, cell scratch test and qPCR were performed to confirm the occurrence of replicative senescence in PDLSCs during passaging. Three groups of cells at passage 4 (P4), passage 10 (P10) and passage 20 (P20) were collected for non-targeted metabolomics analysis. Metabonomic sequencing showed that the metabolism of replicative senescence in PDLSCs varied significantly. In particular, the content of fatty acid metabolites decreased with senescence, including capric acid, stearic acid, myristic acid and dodecanoic acid. KEGG pathway analysis showed that the AMPK signaling pathway was closely related to AMP levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK and the profile of FOXO1 and FOXO3a, which are downstream of the AMPK signaling pathway, decreased with senescence. We treated PDLSCs with AICAR, an activator of the AMPK pathway, and the phosphorylated AMPK level at P20 PDLSCs was partially restored. </p><p><strong>CONCLUSION:</strong> In summary, our study suggests that the metabolic process of PDLSCs is active in the early stage of senescence, prefers to consume fatty acids, and is attenuated in the later stages of senescence. AMP accumulates in replicative senescent PDLSCs; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism. Our findings provide a new basis for the clinical application of periodontal ligament stem cells.</p>
2022-11-15 | MTBLS4568 | MetaboLights
Project description:Senescent is an irreversible form of cell cycle arrest initiated by damaged cell constituents and subsequent pro-oncogenic signaling. Replicative senescence in vitro can be considered a model for human aging. When fibroblasts are cultured under atmospheric oxygen conditions of 20%, typical of normal tissue culture procedure, fibroblasts generally reach their replicative capacity at 50-60 population doublings (PDs). When fibroblasts are cultured under normal physiological oxygen conditions of 3%, PDs increase about 30% relative to atmospheric levels. Hence while oxygen is a requirement for normal aerobic respiration, it can contribute to the total amount of oxidative stress to which cells are exposed to, leading to a long-term adverse effect in vitro. Inasmuch, cultures maintained under hyperoxic and hypoxic conditions provide a convenient model system for assessing the relationship between oxygen/oxidative stress and senescence. We used microarrays to profile the changes in global gene expression during aging and senescence of Imr90 cells under growth oxygen conditions of 3% and 20%. Imr90 cells at various population doubling timepoints (young, old, and senescent) grown separately under 3 and 20% oxygen growth conditions were selected for RNA extraction and hybridization on Affymetrix microarrays. Timepoints from cells grown under 3% and 20% oxygen conditions were age matched via population doublings to ensure accurate cross sample comparison.
2010-03-06 | E-GEOD-19018 | biostudies-arrayexpress
Project description:Transcription profiling from human primary fibroblasts as they progress into senescence. Samples were taken early population doubling onwards until cells reached replicative senescence and stopped dividing. Population doubling values are contained in Characteristics[generation] column.
2014-06-17 | E-MTAB-2086 | biostudies-arrayexpress
Project description:Microarrays analysis identifies WNT16in senescent fibroblasts. To identify genes expressed in replicative senescence, microarray experiments were conducted in which we compared the RNA expression profile of young MRC5 fibroblasts at population doubling 28 (PDL28) and replicative senescent MRC5 fibroblasts at PDL63. In total, 177 gene probes were upregulated and 338 gene probes were downregulated in senescent versus young MRC5 fibroblasts. Genes were classified based on mapping to KEGG pathways. Upregulated genes were enriched in three KEGG pathways, the Wingless-type MMTV integration site (WNT) signaling pathway (WNT16, PLCB4, CCND2, SFRP1, WNT5B, RAC2), cytokine-cytokine receptor interaction (TNFRSF10D, TNFRSF10B, TNFRSF10C, IL1R2, IL18, VEGFC), and the p53 signaling pathway (CDKN1A, TNFRSF10B, PERP, STEAP3, ZMAT3). Repressed genes were enriched in three KEGG pathways, cell cycle (PKMYT1, CDC7, CCNE2, MCM4, BUB1, CDC25A, CDKN1B, MCM6, PLK1, CDKN2C, CCNB2, MCM3, BUB1B, CCNA2, CDC2), cytokine-cytokine receptor interaction (KITLG, IL11, TNFSF4, CCL2, PDGFRA, TNFRSF11B, TGFBR1, IL1R1, TNFRSF19), and DNA replication (POLE, RFC2, MCM4, RNASEH2B, POLA1, DNA2, MCM6, PRIM1, RFC4, MCM3). Along with p53 transcriptional targets (CDKN1A, PERP, WIG1), genes encoding secreted factors (WNT16, MMP10, MMP3) were among the most strongly increased in senescent cells.
2009-12-15 | GSE15919 | GEO
Project description:Noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, and a wide range of long noncoding RNAs (lncRNAs). Although many lncRNAs have been identified, only a small number of lncRNAs have been characterized functionally. Here, we sought to identify lncRNAs differentially expressed during replicative senescence. We compared lncRNAs expressed in proliferating, early-passage, 'young' human diploid WI-38 fibroblasts [population doubling (PDL) 20] with those expressed in senescent, late-passage, 'old' fibroblasts (PDL 52) by RNA sequencing (RNA-Seq). Numerous transcripts in all lncRNA groups (antisense lncRNAs, pseudogene-encoded lncRNAs, previously described lncRNAs and novel lncRNAs) were validated using reverse transcription (RT) and real-time, quantitative (q)PCR. Among the novel senescence-associated lncRNAs (SAL-RNAs) showing lower abundance in senescent cells, SAL-RNA1 (XLOC_023166) was found to delay senescence, because reducing SAL-RNA1 levels enhanced the appearance of phenotypic traits of senescence, including an enlarged morphology, positive β-galactosidase activity, and heightened p53 levels. Our results reveal that the expression of known and novel lncRNAs changes with senescence and suggests that SAL-RNAs play direct regulatory roles in this important cellular process. RNA was extracted from both young and senescent WI-38 cells and used for total RNA-Seq.
2016-02-08 | E-GEOD-77675 | biostudies-arrayexpress
Project description:Cellular senescence is classified into two types; replicative and premature senescence. Gene expression and epigenetic changes are different in types of senescence, replicative and premature senescence, and cell types. Normal human diploid fibroblast TIG-3 cells were often used in cellular senescence research, however, their epigenetic profiles were not fully understood. To elucidate how cellular senescence is epigenetically regulated in TIG-3 cells, we analyzed gene expression and DNA methylation profiles among three types of senescent cells, namely, replicative senescent, RAS-induced senescent (RIS) and non-permissive temperature-induced senescent SVts8 cells, using gene expression and methylation microarrays. The expression of genes involved in cell cycle and immune response were commonly either down- or up-regulated among three types of senescent cells, respectively. The sequential alteration of DNA methylation level was observed only in replicative senescent cells in a time-dependent manner, but not in premature senescent cells. The integrated analysis of gene expression and methylation in replicative senescent cells demonstrated that the expression of 759 genes involved in cell cycle and immune response was associated with methylation. Furthermore, hypomethylation occurred at non-CpG island regions (open sea) on the genes with increased expression as well as non-CpG promoter of the genes related to immune response. Several miRNAs regulated by DNA methylation were found to affect the expression of their target genes. Taken together, these results indicate that DNA methylation contributes to introduction and establishment of replicative senescence partly by regulating gene expression.
2017-02-12 | GSE81797 | GEO
Project description:Cellular senescence is classified into two types; replicative and premature senescence. Gene expression and epigenetic changes are different in types of senescence, replicative and premature senescence, and cell types. Normal human diploid fibroblast TIG-3 cells were often used in cellular senescence research, however, their epigenetic profiles were not fully understood. To elucidate how cellular senescence is epigenetically regulated in TIG-3 cells, we analyzed gene expression and DNA methylation profiles among three types of senescent cells, namely, replicative senescent, RAS-induced senescent (RIS) and non-permissive temperature-induced senescent SVts8 cells, using gene expression and methylation microarrays. The expression of genes involved in cell cycle and immune response were commonly either down- or up-regulated among three types of senescent cells, respectively. The sequential alteration of DNA methylation level was observed only in replicative senescent cells in a time-dependent manner, but not in premature senescent cells. The integrated analysis of gene expression and methylation in replicative senescent cells demonstrated that the expression of 759 genes involved in cell cycle and immune response was associated with methylation. Furthermore, hypomethylation occurred at non-CpG island regions (open sea) on the genes with increased expression as well as non-CpG promoter of the genes related to immune response. Several miRNAs regulated by DNA methylation were found to affect the expression of their target genes. Taken together, these results indicate that DNA methylation contributes to introduction and establishment of replicative senescence partly by regulating gene expression.
2017-02-12 | GSE81788 | GEO
Project description:Cellular senescence is classified into two types; replicative and premature senescence. Gene expression and epigenetic changes are different in types of senescence, replicative and premature senescence, and cell types. Normal human diploid fibroblast TIG-3 cells were often used in cellular senescence research, however, their epigenetic profiles were not fully understood. To elucidate how cellular senescence is epigenetically regulated in TIG-3 cells, we analyzed gene expression and DNA methylation profiles among three types of senescent cells, namely, replicative senescent, RAS-induced senescent (RIS) and non-permissive temperature-induced senescent SVts8 cells, using gene expression and methylation microarrays. The expression of genes involved in cell cycle and immune response were commonly either down- or up-regulated among three types of senescent cells, respectively. The sequential alteration of DNA methylation level was observed only in replicative senescent cells in a time-dependent manner, but not in premature senescent cells. The integrated analysis of gene expression and methylation in replicative senescent cells demonstrated that the expression of 759 genes involved in cell cycle and immune response was associated with methylation. Furthermore, hypomethylation occurred at non-CpG island regions (open sea) on the genes with increased expression as well as non-CpG promoter of the genes related to immune response. Several miRNAs regulated by DNA methylation were found to affect the expression of their target genes. Taken together, these results indicate that DNA methylation contributes to introduction and establishment of replicative senescence partly by regulating gene expression.
2017-02-12 | GSE81786 | GEO
Project description:Transcription profiling from young and pre-senescent IMR90 cells, transfected either with hTERT (pBabe-puro-hTERT) or vector control (pBabe-puro). Population doubling values are contained in Characteristics[generation] column.
2014-06-17 | E-MTAB-2087 | biostudies-arrayexpress