Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Conserved transcriptomic signatures and protein markers in cellular senescence models

ABSTRACT: Cellular senescence is described as an irreversible cell cycle arrest induced in response to various stresses. Senescent cells are characterised by heterogeneous signalling alterations, complex secretory phenotype, known as senescence-associated secretory phenotype (SASP), and diverse transcriptomic profile. With the aim to investigate senescence heterogeneity and identify conserved transctiptomic alterations and universal senescence markers, we performed RNA-seq and multiplex proteomic analysis in proteasome inhibition-induced and stress-induced premature senescence models of HFL1 and BJ human fibroblasts. Our data revealed diverse transcriptomic signatures, but also, 231 common differentially expressed genes related to cell division and ECM remodelling, and enriched pathways that remained conserved among the different models with senescence onset. Moreover, we identified a subset of proteins and validated them in replicative senescent models. These proteins are involved in cell cycle arrest and promote a pro-inflammatory environment in premature and replicative senescence models. We suggest that the simultaneous analysis of p21, p-c-JUN, BCL-xL and survivin in cellular lysates, and IL-8, GM-CSF, GDF-15 and GROa in culture supernatants can provide a powerful tool for the identification and monitoring of senescent cells and can support the assessment of the efficacy of potential senotherapeutic approaches.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235768 | GEO | 2023/07/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Senescence of endothelial cells promotes phenotypic changes in adventitial fibroblasts: possible implications for vascular aging

Project description:Aging is the most important risk factor for the development of cardiovascular diseases. Senescent cells release plethora of factors commonly known as the senescence-associated secretory phenotype (SASP), which can modulate the normal function of the vascular wall. It is currently not well understood if and how endothelial cell senescence can affect adventitial niche. The aim of this study was to characterize oxidative stress-induced endothelial cells senescence and identify their paracrine effects on the primary cell type of the adventitia, the fibroblasts. Human aortic endothelial cells (HAEC) were treated with hydrogen peroxide to induce premature senescence. Mass spectrometry analysis identified several proteomic changes in senescent HAEC with top upregulated secretory protein growth differentiation factor 15 (GDF-15). Treatment of the human adventitial fibroblast cell line (hAdv cells) with conditioned medium (CM) from senescent HAEC resulted in alterations in the proteome of hAdv cells identified in mass spectrometry analysis. Majority of differentially expressed proteins in hAdv cells treated with CM from senescent HAEC were involved in the uptake and metabolism of lipoproteins, mitophagy and ferroptosis. We next analyzed if some of these changes and pathways might be regulated by GDF-15. We found that recombinant GDF-15 affected some ferroptosis-related factors (e.g. ferritin) and decreased oxidative stress in the analyzed adventitial fibroblast cell line, but it had no effect on erastin-induced cell death. Contrary, silencing of GDF-15 in hAdv cells was protective against this ferroptotic stimuli. Our findings provide a better understanding of the biology of senescent cells and can be of importance for potential therapeutic strategies targeting cell senescence or ferroptosis to alleviate vascular diseases.

2024-02-13 | MSV000094069 | MassIVE

Potential roles of DNA methylation in the initiation and establishment of replicative senescence revealed by array-based methylome and transcriptome analyses [methylation 450K]

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

Potential roles of DNA methylation in the initiation and establishment of replicative senescence revealed by array-based methylome and transcriptome analyses [methylation]

2017-02-12 | GSE81788 | GEO

Potential roles of DNA methylation in the initiation and establishment of replicative senescence revealed by array-based methylome and transcriptome analyses [expression]

2017-02-12 | GSE81786 | GEO

The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress [scRNA-seq]

Project description:Sublethal cell damage can trigger a complex adaptive program known as senescence, characterized by growth arrest, resistance to apoptosis, and a senescence-associated secretory phenotype (SASP). As senescent cells accumulating in aging organs are linked to many age-associated diseases, senotherapeutic strategies are actively sought to eliminate them. Here, a whole-genome CRISPR knockout screen revealed that proteins in the YAP-TEAD pathway influenced senescent cell viability. Accordingly, treating senescent cells with a drug that inhibited this pathway, Verteporfin (VPF), selectively triggered apoptotic cell death and derepressed DDIT4, in turn inhibiting mTOR. Reducing mTOR function in senescent cells diminished endoplasmic reticulum (ER) biogenesis, causing ER stress and apoptosis due to high demands on ER function by the SASP. Importantly, VPF treatment decreased senescent cell numbers in the organs of old mice and mice exhibiting doxorubicin-induced senescence. We present a novel senolytic strategy that eliminates senescent cells by hindering ER activity required for SASP production.

2023-07-13 | GSE221117 | GEO

The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress [bulk RNA-seq]

2023-07-13 | GSE221104 | GEO

The YAP-TEAD complex promotes senescent cell survival by lowering endoplasmic reticulum stress [scRNA-seq_mouse]

2023-07-13 | GSE232273 | GEO

Oxylipin biosynthesis reinforces cellular senescence through a RAS/p53 feedback loop and allows detection of senolysis

Project description:Cellular senescence is a stress or damage response that causes a permanent proliferative arrest and secretion of numerous factors with potent biological activities. This senescence-associated secretory phenotype (SASP) has been characterized largely for secreted proteins that participate in embryogenesis, wound healing, inflammation and many age-related pathologies. By contrast, lipid components of the SASP are understudied. We show that senescent cells activate the biosynthesis of several oxylipins that promote segments of the SASP and reinforce the proliferative arrest. Notably, senescent cells synthesize and accumulate an unstudied intracellular prostaglandin, 1a,1b-dihomo-15-deoxy-delta-12,14-prostaglandin J2. Released 15-deoxy-delta-12,14-prostaglandin J2 is a biomarker of senolysis in culture and in vivo. This and other prostaglandin D2-related lipids promote the senescence arrest and SASP by activating RAS signaling. These data identify an important aspect of cellular senescence and a method to detect senolysis

2021-02-20 | ST001708 | MetabolomicsWorkbench

Potential roles of DNA methylation in the initiation and establishment of replicative senescence revealed by array-based methylome and transcriptome analyses

Project description:Cellular senescence is classified into two groups; replicative and premature senescence. The gene expression and epigenetic changes differ between two groups of senescence, replicative and premature senescence, and cell types. Normal human diploid fibroblast TIG-3 cells have often been used in cellular senescence research, however, their epigenetic profiles are not fully understood. To elucidate how cellular senescence is epigenetically regulated in TIG-3 cells, we analyzed the gene expression and DNA methylation profiles of 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 the cell cycle and immune response was commonly either down- or up-regulated in the three types of senescent cells, respectively. The sequential alteration of the DNA methylation level in a time-dependent manner was observed in replicatively senescent cells, but not in premature senescent cells. The integrated analysis of gene expression and methylation in replicatively senescent cells demonstrated that the expression of 759 genes involved in the cell cycle and immune response was associated with methylation. Furthermore, hypomethylation occurred in non-CpG island regions (open sea) of the genes exhibiting increased expression as well as non-CpG island promoters of the genes related to the immune response. Several miRNAs regulated through DNA methylation were found to affect the expression of their target genes. Taken together, these results indicate that DNA methylation contributes to the introduction and establishment of replicative senescence partly by regulating gene expression.

2017-02-12 | GSE90942 | GEO

Expression data from control infected and H-RASG12V infected IMR90 cells.

Project description:Cellular senescence is a stable proliferation arrest associated with an altered secretory pathway, the Senescence-Associated Secretory Phenotype (SASP). However, cellular senescence is initiated by diverse molecular triggers, such as activated oncogenes and shortened telomeres, and is associated with varied and complex physiological endpoints, such as tumor suppression and tissue aging. The extent to which distinct triggers activate divergent modes of senescence that might be associated with different physiological endpoints is largely unknown. To begin to address this, we performed gene expression profiling to compare the senescence programs associated with two different modes of senescence, oncogene-induced senescence (OIS) and replicative senescence (RS [in part caused by shortened telomeres]). While both OIS and RS are associated with many common changes in gene expression compared to control proliferating cells, they also exhibit substantial differences. These results are discussed in light of potential physiological consequences, tumor suppression and aging. We used microarrays to detail the global programme of gene expression after oncogene induced senescence.

2014-02-28 | E-GEOD-54402 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data