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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- Staphylococcus aureus
- 12 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
Treatment of stationary growth phase Staphylococcus aureus SA113 with 100-fold of the MIC of the lipopeptide antibiotic daptomycin leaves alive a small fraction of drug tolerant albeit genetically susceptible bacteria. This study shows that cells of this subpopulation exhibit active metabolism even hours after the onset of the drug challenge. Isotopologue profiling using fully 13C-labeled glucose revealed de novo biosynthesis of the amino acids Ala, Asp, Glu, Ser, Gly and His. The isotopologue composition in Asp and Glu suggested an increased activity of the TCA cycle under daptomycin treatment compared to unaffected stationary growth phase cells. Microarray analysis showed differential expression of specific genes 10 minutes and 3 hours after addition of the drug. Besides factors involved in drug response, a number of metabolic genes appear to shape the signature of daptomycin-tolerant S. aureus cells. These observations will be useful towards the development of new strategies against persisters and related forms of bacterial cells with downshifted physiology.
Publication Title
Metabolic and transcriptional activities of Staphylococcus aureus challenged with high-doses of daptomycin.
Sample Metadata Fields
No sample metadata fields
View Samples- Staphylococcus aureus
- 6 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
For Staphylococcus aureus it was shown previously that aminocoumarinecoumarin antibiotics such as novobiocin lead to immediate down-regulation of recA expression and thereby inhibition of the SOS response, the mutation frequency and the recombination capacity. Aminocoumarinecoumarin function by inhibition of the ATPase activity of the gyrase subunit B. Here we analysed the global impact of the DNA relaxing agent novobiocin on gene expression in S. aureus. By use of a novobiocin resistant mutant, it became evident that the change in recA expression is due to gyrase inhibition. Microarray analysis and Northern blot hybridization revealed that the expression of a distinct set of genes is increased (e.g. recF-gyrB-gyrA, rib operon and ure operon )), or decreased (e.g. arlRS, recA, lukA, hlgC, fnbA) by novobiocin. The two-component ArlRS system was previously found to decrease the supercoiling level in S. aureus. Thus, down-regulation of arlRS might in part compensate for the relaxing effect of novobiocin. Novobiocin resulted in down-regulation of several of arlRS repressed target genes in an arl mutant. Global analysis and gene mapping of supercoiling sensitive genes did not give indications that they are clustered in the genome. Promoter fusion assays confirmed that responsiveness of a given gene is intrinsic to the promoter region but independent of the chromosomal location. The results indicate that molecular property of the spacers of a given promoter dictatesa given promoter rather than chromosomal topology dictates the responsiveness towards changes in supercoiling rather than chromosomal topology.
Publication Title
Altering gene expression by aminocoumarins: the role of DNA supercoiling in Staphylococcus aureus.
Sample Metadata Fields
Treatment
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Models for tumorigenesis can be made by transforming normal cells with defined genetic elements. This allows us to determine that adrenocortical tumor development and progression follows a multistep model. Morever, we demonstrated that the order of genetic events has a great consequence on the phenotype of the resultant tumor. We performed transcriptomic analysis using cDNA microarrays to identify the molecular signature that might explain the distinctive in vivo phenotypes observed in response to both orders of the mutational events.
Publication Title
Acquisition order of Ras and p53 gene alterations defines distinct adrenocortical tumor phenotypes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To identify proteins regulated by glucose through changes in their rate of protein synthesis, translational profiling of MIN6 cells acutely incubated at either low or high glucose concentration was performed (i.e. microarray analysis was performed on mRNAs associated with polysomes, as an increase in the association of mRNA with polysomes is indicative of an increase in the rate of initiation step of translation and hence an increase in protein expression) (Johannes et al., 1999; Mikulits et al., 2000).
Publication Title
Distinct glucose-dependent stress responses revealed by translational profiling in pancreatic beta-cells.
Sample Metadata Fields
Specimen part, Cell line, Compound, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) was partially resistant to etoposide and daunorubicin as compared to empty vector infected control cells (U937_vec). Similarly, inducible expression of EVI1 in HL-60 cells decreased their sensitivity to daunorubicin. Gene expression microarray analyses of U937_EVI1 and U937_vec cells cultured in the absence or presence of etoposide showed that 77 and 419 genes were regulated by EVI1 and etoposide, respectively. Notably, mRNA levels of 26 of these genes were altered by both stimuli, indicating that EVI1 regulated genes were strongly enriched among etoposide regulated genes and vice versa. One of the genes that were induced by both EVI1 and etoposide was CDKN1A/p21/WAF, which in addition to its function as a cell cycle regulator plays an important role in conferring chemotherapy resistance in various tumor types. Indeed, overexpression of CDKN1A in U937 cells mimicked the phenotype of EVI1 overexpression, similarly conferring partial resistance to antileukemic drugs.
Publication Title
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
While prion infections have been extensively characterized in the laboratory mouse, little is known regarding the molecular responses to prions in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage of mouse RML prions. Here we describe the accumulation of prions and associated pathology in the rat and describe the transcriptional impact throughout prion disease. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular processes are unfolding in response to prion infection. At the level of individual transcripts, however, variability exists between mice and rats and many genes deregulated in mouse scrapie are not affected in rats. Notwithstanding these differences, many transcriptome responses are conserved between mice and rats infected with scrapie. Our findings highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular.
Publication Title
Transcriptomic responses to prion disease in rats.
Sample Metadata Fields
Specimen part, Disease
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
HIV Tg rats exhibit pulmonary hypertension and pulmonary artery remodeling. In an effort to begin to understand cell signaling pathways which are altered in lungs from HIV transgenic rats, we used microarray analysis.
Publication Title
Human immunodeficiency virus transgenic rats exhibit pulmonary hypertension.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 2 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Muscle tissue was longitudinally characterized histologically for electron transport function by staining 1mm of quadriceps muscle at 70 micron intervals for the activities of two complexes in the mitochondrial electron transport chain, Cytochrome C Oxidase and Succinate Dehydrogenase. Unstained serial cryosections were prepared for Laser Capture Microdissection. Target cells from the serial sections were isolated and pooled for RNA extraction, amplification and hybridization on Affymetrix microarrays. We selected homogeneous populations of muscle fibers for expression profiling based upon the presence/absence of electron transport dysfunction caused by the somatic accumulation of mitochondrial DNA deletion mutations.
Publication Title
Mitochondrial biogenesis drives a vicious cycle of metabolic insufficiency and mitochondrial DNA deletion mutation accumulation in aged rat skeletal muscle fibers.
Sample Metadata Fields
Age, Specimen part
View Samples