The effect of CD153 engagement on the activation of senescence-associated (SA) T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA773036 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16499251_1.fastq.gz | Fastqsanger.gz | |||
| SRR16499251_2.fastq.gz | Fastqsanger.gz | |||
| SRR16499252_1.fastq.gz | Fastqsanger.gz | |||
| SRR16499252_2.fastq.gz | Fastqsanger.gz | |||
| SRR16499253_1.fastq.gz | Fastqsanger.gz |
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Project description:Advancing age is associated with the increase and accumulation of unique lymphocyte populations. Among them, CD153+ PD-1+ CD4+ T cells (SA-T cells) may underlie the pathogenesis of autoimmune and chronic inflammatory diseases. To assess the possible involvement of CD153 in regulating the cellular function, we performed bulk RNA-seq analysis.
2022-09-20 | GSE186221 | GEO
Project description:Pluripotent stem cells evade replicative senescence, whereas other primary cells lose their proliferation and differentiation potential after a limited number of cell divisions M-bM-^@M-^S and this is accompanied by specific senescence-associated DNA methylation (SA-DNAm) changes. Here, we investigate SA-DNAm changes in mesenchymal stromal cells (MSC) upon long-term culture, irradiation-induced senescence, immortalization and reprogramming into induced pluripotent stem cells (iPSC) using high density HumanMethylation450 BeadChips. SA-DNAm changes are highly reproducible and occur particularly in intergenic and non-promoter regions of developmental genes. We demonstrate that ionizing irradiation, although associated with a very similar senescence phenotype, does not affect SA-DNAm. Furthermore, overexpression of the catalytic subunit of the human telomerase (TERT) or conditional immortalization with a doxycycline-inducible system (TERT and SV40 TAg) result in telomere extension but do not influence SA-DNAm. In contrast, we demonstrate that reprogramming into iPSC prevented SA-DNAm changes. Our results indicate that replicative senescence is associated with an epigenetically controlled process which stalls cells in a particular differentiated state, whereas irradiation-induced senescence and immortalization are not causally related to this process. Absence of SA-DNAm in pluripotent cells may play a central role for their escape from cellular senescence. Samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2012-09-24 | E-GEOD-37066 | biostudies-arrayexpress
Project description:Pluripotent stem cells evade replicative senescence, whereas other primary cells lose their proliferation and differentiation potential after a limited number of cell divisions – and this is accompanied by specific senescence-associated DNA methylation (SA-DNAm) changes. Here, we investigate SA-DNAm changes in mesenchymal stromal cells (MSC) upon long-term culture, irradiation-induced senescence, immortalization and reprogramming into induced pluripotent stem cells (iPSC) using high density HumanMethylation450 BeadChips. SA-DNAm changes are highly reproducible and occur particularly in intergenic and non-promoter regions of developmental genes. We demonstrate that ionizing irradiation, although associated with a very similar senescence phenotype, does not affect SA-DNAm. Furthermore, overexpression of the catalytic subunit of the human telomerase (TERT) or conditional immortalization with a doxycycline-inducible system (TERT and SV40 TAg) result in telomere extension but do not influence SA-DNAm. In contrast, we demonstrate that reprogramming into iPSC prevented SA-DNAm changes. Our results indicate that replicative senescence is associated with an epigenetically controlled process which stalls cells in a particular differentiated state, whereas irradiation-induced senescence and immortalization are not causally related to this process. Absence of SA-DNAm in pluripotent cells may play a central role for their escape from cellular senescence.
2012-09-24 | GSE37066 | GEO
Project description:We used microarrays to identify genes that respond to SA differently during the subjective morning and subjective night.
2015-06-22 | GSE61059 | GEO
Project description:Senescence is a universal barrier to immortalisation and tumorigenesis. As such, interest in the use of senescence-induction in a therapeutic context has been gaining momentum in the past few years; however, senescence and immortalisation remain underserved areas for drug discovery owing to a lack of robust senescence inducing agents and an incomplete understanding of the signalling events underlying this complex process. In order to address this issue we undertook a large-scale morphological siRNA screen for inducers of senescence phenotypes in the human melanoma cell line A375P. Following rescreen and validation in a second cancer cell line, HCT116 colorectal carcinoma, a panel of 16 of the most robust hits were selected for further validation based on significance and the potential to be targeted by drug-like molecules. Using secondary assays for detection of senescence biomarkers p21, 53BP1 and senescence associated beta-galactosidase (SA?Gal) in a panel of HCT116 cell lines carrying cancer-relevant mutations, we show that partial senescence phenotypes can be induced to varying degrees in a context dependent manner, even in the absence of p21 or p53 expression. However, proliferation arrest varied among genetic backgrounds with predominantly toxic effects in p21 null cells, while cells lacking PI3K mutation failed to arrest. Furthermore, we show that the oncogene ECT2 is a robust inducer of senescence in all mutant backgrounds tested and highlight a dependence on activating KRASG13D for growth suppression and a complete senescence response, suggesting a potential mechanism to target mutant KRAS signalling through ECT2 in cancers that are reliant on activating KRAS mutations and remain refractory to current treatments.
2017-07-27 | GSE100459 | GEO
Project description:We investigated the role of AMPK activation in the progression of senescence in HFDPCs. The anti-senescence effects of adenine, a recently identified AMPK activator, were determined in a comparison with AICAR, a pharmacological AMPK activator, in HFDPCs. The results showed that either adenine or AICAR induced phosphorylation of Thr172 of AMPK in HFDPCs. As revealed by microarray analysis, significant changes of gene expression pattern were observed in the high-passage HFDPCs compared with that at lower passage level. A chip study using total RNA recovered from three separate wild-type cultures of Human follicle dermal papilla cells (HFDPCs) and three separate cultures of a triple adenine-treated cells.
2014-11-01 | E-GEOD-62798 | biostudies-arrayexpress
Project description:As normal cells approach their proliferative limit, they arrest to undergo replicative senescence, displaying large cell size, flat morphology and activation of senescence-associated beta-galactosidase (SA-b-Gal). A subset of normal or tumor cells exposed in vitro or in vivo to chemotherapy agents such as etoposide perform a related response with a similar cellular phenotype dubbed therapy-induced senescence (TIS). High cellular heterogeneity in samples including TIS cells can impede confident determination of senescence-specific factors, frustrating discovery of markers and targets for functional analysis. As a TIS study model, we treated murine melanoma cells with the chemotherapeutic etoposide, applied a live-cell fluorescent SA-b-Gal senescence assay, and utilized fluorescence-activated cell sorting (FACS) to enrich TIS cells. Enriched senescent cell samples were subjected to mass spectrometry and label-free quantitative proteomics analysis, alongside proliferating and quiescent cell samples. Systems biology analysis revealed that senescent cells overexpress proteins and pathways regulating glycolipid processing, lipid metabolism, and lipid peroxidation. Senescence-associated activation of numerous glycosidases was observed, along with elevated cell surface expression of several major lipid regulatory proteins. Senescent cells were found to contain abundant lipid droplets and to import various types of extracellular lipids in correlation with extent of SA-b-Gal expression, and tumor cells were observed to spontaneously senesce in the presence of excess ceramide or triglycerides. Redox-induced lipid peroxidation, resulting in accumulation of cellular reactive aldehydes and consequent expression of aldehyde detoxification enzymes, was observed to be a key feature of TIS induced by three DNA-damaging chemotherapeutics.
2017-11-06 | PXD006216 | Pride
Project description:Aging leads to a progressive functional decline of the immune system, rendering the elderly increasingly susceptible to disease and infection. The degree to which immune cell senescence contributes to this decline remains unclear, however, since markers that label immune cells with classical features of cellular senescence accurately and comprehensively have not been identified. Using a second‐generation fluorogenic substrate for β‐galactosidase and multi‐parameter flow cytometry, we demonstrate here that peripheral blood mononuclear cells (PBMCs) isolated from healthy humans increasingly display cells with high senescence‐associated β‐galactosidase (SA‐βGal) activity with advancing donor age. The greatest age‐associated increases were observed in CD8+ T‐cell populations, in which the fraction of cells with high SA‐βGal activity reached average levels of 64% in donors in their 60 s. CD8+ T cells with high SA‐βGal activity, but not those with low SA‐βGal activity, were found to exhibit features of telomere dysfunction‐induced senescence and p16‐mediated senescence, were impaired in their ability to proliferate, developed in various T‐cell differentiation states, and had a gene expression signature consistent with the senescence state previously observed in human fibroblasts. Based on these results, we propose that senescent CD8+ T cells with classical features of cellular senescence accumulate to levels that are significantly higher than previously reported and additionally provide a simple yet robust method for the isolation and characterization of senescent CD8+ T cells with predictive potential for biological age.
2021-04-14 | GSE169009 | GEO
Project description:Aging is the primary risk factor for Parkinson’s disease (PD), and astrocyte senescence, or astrosenescence, has emerged as a potential mechanism through which aging may progressively impair glial homeostatic neuronal support and render the brain more vulnerable to neurodegeneration. Yet human experimental models that specifically recapitulate astrosenescence within a PD-relevant genetic background are lacking. Here, we applied passage-induced replicative exhaustion to human iPSC-derived neuroepithelial stem cells (NESCs) from healthy donors and LRRK2 G2019S PD patients to establish an in vitro midbrain aging model. Extended passaging induced senescence-associated changes in NESCs, including reduced proliferative capacity, apoptosis resistance, reduction in telomerase activity, and sustained DNA damage response (DDR) activation, while preserving ventral midbrain identity and differentiation potential. Astrocytes derived from aged progenitors recapitulated multiple senescence hallmarks, including increase in SA-β-gal activity, nuclear lamina disruption, persistent DDR activation, and alteration in mitochondrial homeostasis. In human midbrain organoids (hMOs), passage-induced aging was associated with astrocyte-specific DDR activation, widespread lipidomic remodeling, and a selective reduction of dopaminergic neuron content in LRRK2 G2019S organoids compared to healthy donor-derived organoids. Multi-modal analysis of NESCs, astrocytes, and hMOs further revealed that the LRRK2 G2019S genetic background not only shifts baseline cellular states toward an aged-like profile but actively reshapes aging trajectories in a cell-type- and feature-dependent manner. Together, this work establishes a human iPSC-based midbrain model recapitulating key features of cellular senescence in both healthy and LRRK2 G2019S contexts and provides an in vitro platform to investigate the contribution of astrosenescence to PD-related neurodegeneration.
2026-06-17 | GSE331395 | GEO