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GSE33710
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Senescence in WI-38 cell context was induce by RASv12 over expression Cellular senescence is a permanent cell cycle arrest that is triggered by cancer- initiating or promoting events in mammalian cells and is now considered a major tumour suppressor mechanism. Here, we did a transcriptomic analysis and compared WI-38 contol wich is a human fibroblaste cell line and WI-38 that overexpressed RASv12 a G protein that induce senescence. The goal of our project is to compare transciptomic profile of human growing fibroblast (WI-38 control) and senescent human fibroblast (WI-38 OERAS)
Publication Title
Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
Description
In humans, there are four Ago proteins (Ago1–4) and AGO1- and 2 were previously implicated in TGS induced by exogenous siRNAs and microRNAs (miRs) directed against gene promoter transcripts via promotion of changes in histone covalent modifications and DNA methylation. Not-with-standing, many mechanistic details of this process remain poorly defined in human cells, and very little is known about the identity of possible endogenous signals, which may drive this process in human cells. Given the evolutionary conserved role of siRNAs and AGO proteins in TGS and heterochromatin formation, we set out to analyse their possible involvement in senesence-associated repression of E2F target genes. To obtain a detailed picture of AGO-immunoprecipitating miRs (RIP) in senescent cells, we used next-generation sequencing (NGS)(RIP-Seq). We also included histone H3 dimethylated on lysine 9 (H3K9me2) in this analysis to assign potential AGO2-interacting miRs to a repressive chromatin state and unfractionated, cellular RNA from senescent cells for normalisation. Overall design: Determination of AGO AGO-immunoprecipitating miRs in WI-38 senescent human fibroblast
Publication Title
Senescence is an endogenous trigger for microRNA-directed transcriptional gene silencing in human cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 96 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) ‘pioneers’ the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications.
Publication Title
AP-1 imprints a reversible transcriptional programme of senescent cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 47 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Treatment induced senescence (TIS) is a terminal cell cycle arrest program, increasingly recognized as a tumor suppressor mechanism complementing apoptosis in response to standard chemotherapy regimens. In particular cells with blocked apoptotic pathways rely on senescence as the only remaining failsafe mechanism to keep the neoplastic growth in check. However, little is known about biological properties, long-term fate of senescent tumor cells and their impact on the microenvironment.
Publication Title
AP-1 imprints a reversible transcriptional programme of senescent cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Senescent cells affect many physiological and pathophysiological processes. While select genetic and epigenetic elements for senescence induction have been identified, the dynamics, epigenetic mechanisms and regulatory networks defining senescence competence, induction and maintenance remain poorly understood, precluding the deliberate therapeutic targeting of senescence for health benefits. Here, we examined the possibility that the epigenetic state of enhancers determines senescent cell fate. We explored this by generating time-resolved transcriptomes and epigenome profiles during oncogenic RAS-induced senescence and validating central findings in different cell biology and disease models of senescence. Through integrative analysis and functional validation, we reveal links between enhancer chromatin, transcription factor recruitment and senescence competence. We demonstrate that activator protein 1 (AP-1) 'pioneers' the senescence enhancer landscape and defines the organizational principles of the transcription factor network that drives the transcriptional programme of senescent cells. Together, our findings enabled us to manipulate the senescence phenotype with potential therapeutic implications.
Publication Title
AP-1 imprints a reversible transcriptional programme of senescent cells.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 2 Downloadable Samples
Affymetrix Human Transcriptome Array 2.0 (hta20), Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select for Different Mesenchymal Stromal Cells.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanMethylation450 BeadChip (HumanMethylation450_15017482), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Culture medium of mesenchymal stromal cells (MSCs) is usually supplemented with either human platelet lysate (HPL) or fetal calf serum (FCS). Many studies have demonstrated that proliferation and cellular morphology is influenced by these additives hence they may favor outgrowth of specific subpopulations, thereby affecting the heterogeneous composition of MSCs. We have isolated and expanded human bone marrow derived MSCs in parallel with HPL or FCS for two passages. In HPL the proliferation was significantly higher and cells reflected more spindle-shaped morphology. Pairwise comparisons of gene expression profiles (Affymetrix HTA 2.0) revealed only moderate differences. When we apply a fold change >1.5 and limma-adjusted P-value of <0.05, only 69 transcripts were differentially expressed. These results indicate that there is no systematic bias for specific subpopulations of MSCs by using either HPL or FCS.
Publication Title
Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select for Different Mesenchymal Stromal Cells.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
Severe malnutrition in young children is associated with signs of hepatic dysfunction such as steatosis and hypoalbuminemia, but its etiology is unknown. To investigate the underlying mechanisms of hepatic dysfunction we used a rat model of malnutrition by placing weanling rats on a low protein or control diet (5% or 20% of calories from protein, respectively) for four weeks. Low protein diet-fed rats developed hypoalbuminemia and severe hepatic steatosis, consistent with the human phenotype. Hepatic peroxisome content was decreased and metabolomic analysis indicated impaired peroxisomal function. Loss of peroxisomes was followed by accumulation of dysfunctional mitochondria and decreased hepatic ATP levels. Fenofibrate supplementation restored hepatic peroxisome abundance and increased mitochondrial fatty acid -oxidation capacity, resulting in reduced steatosis and normalization of ATP and plasma albumin levels. These findings provide important insight into the metabolic
Publication Title
Malnutrition-associated liver steatosis and ATP depletion is caused by peroxisomal and mitochondrial dysfunction.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 503 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a), Affymetrix Human Genome U95B Array (hgu95b), Affymetrix Human Genome U95C Array (hgu95c)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process.
Sample Metadata Fields
Age, Specimen part, Race
View Samples- Homo sapiens
- 196 Downloadable Samples
- Affymetrix Human Genome U95C Array (hgu95c), Affymetrix Human Genome U95A Array (hgu95a), Affymetrix Human Genome U95B Array (hgu95b)
Description
Prostate cancer is characterized by heterogeneity in the clinical course that often does not to correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. The metastatic samples are highly heterogeneous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodeling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer.
Publication Title
Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process.
Sample Metadata Fields
Specimen part
View Samples