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GSE3188
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The response of cells to hypoxia is characterised by co-ordinated regulation of many genes. Studies of the regulation of the expression of many of these genes by oxygen has implicated a role for the heterodimeric transcription factor hypoxia inducible factor (HIF). The mechanism of oxygen sensing which controls this heterodimeric factor is via oxygen dependent prolyl and asparaginyl hydroxylation by specific 2-oxoglutarate dependent dioxygenases (PHD1, PHD2, PHD3 and FIH-1). Whilst HIF appears to have a major role in hypoxic regulation of gene expression, it is unclear to what extent other transcriptional mechanisms are also involved in the response to hypoxia. The extent to which 2-oxoglutarate dependent dioxygenases are responsible for the oxygen sensing mechanism in HIF-independent hypoxic gene regulation is also unclear. Both the prolyl and asparaginyl hydroxylases can be inhibited by dimethyloxalylglycine (DMOG). Such inhibition can produce activation of the HIF system with enhanced transcription of target genes and might have a role in the therapy of ischaemic disease. We have examined the extent to which the HIF system contributes to the regulation of gene expression by hypoxia, to what extent 2-oxoglutarate dependent dioxygenase inhibitor can mimic the hypoxic response and the nature of the global transcriptional response to hypoxia. We have utilised microarray assays of mRNA abundance to examine the gene expression changes in response to hypoxia and to DMOG. We demonstrate a large number of hypoxically regulated genes, both known and novel, and find a surprisingly high level of mimicry of the hypoxic response by use of the 2-oxoglutarate dependent dioxygenase inhibitor, dimethyloxalylglycine. We have also used microarray analysis of cells treated with small interfering RNA (siRNA) targeting HIF-1alpha and HIF-2alpha to demonstrate the differing contributions of each transcription factor to the transcriptional response to hypoxia. Candidate transcripts were confirmed using an independent microarray platform and real-time PCR. The results emphasise the critical role of the HIF system in the hypoxic response, whilst indicating the dominance of HIF-1alpha and defining genes that only respond to HIF-2alpha.
Publication Title
Concordant regulation of gene expression by hypoxia and 2-oxoglutarate-dependent dioxygenase inhibition: the role of HIF-1alpha, HIF-2alpha, and other pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
The aim of the study is to evaluate oxygen regulated gene expression in human peripheral blood lymphocytes using microarray analysis.
Publication Title
Variations within oxygen-regulated gene expression in humans.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Dicamba is an auxin-like herbicide that can stimulate the production of ethylene and ABA biosynthesis. The subsequent stomatal closure and build-up of reactive oxygen species is hypothesized to contribute to plant death.
Publication Title
Mutant analysis in Arabidopsis provides insight into the molecular mode of action of the auxinic herbicide dicamba.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Critically ill preterm infants experience multiple stressors while hospitalized. Morphine is commonly prescribed to ameliorate their pain and stress. We hypothesized that neonatal stress will have a dose-dependent effect on hippocampal gene expression, and these effects will be altered by morphine treatment. Male C57BL/6 mice were exposed to 5 treatment conditions between postnatal day 5 and 9: 1) Control, 2) mild stress + saline, 3) mild stress + morphine, 4) severe stress + saline and 5) severe stress + morphine. Hippocampal RNA was extracted and analyzed using Affymetrix Mouse Gene 1.0 ST Arrays. Single gene analysis and gene set analysis were used to compare groups with validation by qPCR. Stress resulted in enrichment of genes sets related to fear response, oxygen carrying capacity and NMDA receptor synthesis. Morphine downregulated gene sets related to immune function. Stress plus morphine resulted in enrichment of mitochondrial electron transport gene sets, and down-regulation of gene sets related to brain development and growth. We conclude that neonatal stress alone influences hippocampal gene expression, morphine alters a subset of stress-related changes in gene expression and influences other gene sets. Stress plus morphine show interaction effects not present with either stimulus alone. These changes may alter neurodevelopment.
Publication Title
Effects of neonatal stress and morphine on murine hippocampal gene expression.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Rhizoctonia solani is an economically important soil-borne necrotrophic fungal pathogen, with a broad host range and for which little effective resistance exists in crop plants. Arabidopsis is resistant to the R. solani AG8 isolate but susceptible to R. solani AG2-1. Affymetrix microarray analysis was performed to determine genes that are affected in common and specifically by AG8 and AG2-1.
Publication Title
Genetic and genomic analysis of Rhizoctonia solani interactions with Arabidopsis; evidence of resistance mediated through NADPH oxidases.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Hordeum vulgare
- 4 Downloadable Samples
- Affymetrix Barley Genome Array (barley1)
Description
Trancript Based Cloning (TBC) uses standard Gene Expression techniques to quickly isolate genes of interest and begin to determine their function. Using a particular mutant phenotype, identified during a programme of mutagenesis and screning, and a wild-type control we can quickly determine a list of genes that is likely to contain the gene responsible for the phenotype. TBC is a general method for identifying and cloning important plant genes that is fast and may be applicable to almost any plant species Transcript abundance assays on the barley rar1-2 mutant and Sultan5 wild type were performed by using standard methods for the Affymetrix barley genome array (Affymetrix). For each genotype, two independent biological replicates were analyzed and pooled for analysis. Data were analyzed with DCHIP VERSION 1.3 (www.dchip.org),using data from only perfect-match oligonucleotides. Model-based analysis was performed by using perfect match-only analysis, compiling data from two biological replicates for each condition. Pairwise comparisons were analyzed for each condition, and a lower 90% confidence bound (LCB) and fold change were determined for each comparison. Gene expression changes were considered significant if the LCB was 1.4-fold or higher and if the intensities between the two conditions differed by >100. ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, james hadfield. The equivalent experiment is BB5 at PLEXdb.]
Publication Title
A Ca2+/calmodulin-dependent protein kinase required for symbiotic nodule development: Gene identification by transcript-based cloning.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Reactive oxygen species such as hydrogen peroxide (H2O2) are important in biotic and abiotic stress responses in plants, but their source is often unclear. We have identified an Arabidopsis mutant that shows loss of stress responsive GSTF8 gene expression in response to the plant defence signal salicylic acid (SA) . The mutant showed increased susceptibility to both fungal and bacterial pathogens. The dsr1 mutation was mapped to mitochondrial succinate dehydrogenase (SDH1-1) and dsr1 had reduced SDH activity and a lowered mitochondrial H2O2 production.
Publication Title
Mitochondrial complex II has a key role in mitochondrial-derived reactive oxygen species influence on plant stress gene regulation and defense.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Maternal 5-HT1A-receptor (R) is required for the timely development of the hippocampus and the establishment of emotional behaviors in Swiss-Webster (SW) mice. A partial and/or complete loss of maternal 5-HT1AR results in delayed ventral dentate granule cell (v-DGC) development and subsequent anxiety-like phenotype in the wild-type offspring by a non-genetic, presumably epigenetic mechanism. Here we tested v-DGCs for genome-wide DNA methylation changes elicited by the receptor deficient maternal environment. We identified a set of hypomethylated regions in the offspring of receptor deficient mothers. A significant fraction of these maternal-differentially methylated regions (m-DMRs) mapped to strong CpG islands, sequences that are typically not methylated or if methylated, resistant to environmental-induced changes. Many m-DMRs mapped to exons and some were associated with expression changes. Their hypomethylation was due to an arrest in de novo methylation and, to a lesser extent, to demethylation during postnatal life indicating that the perturbation in methylation coincides with the developmental delay in DGC maturation in the offspring of receptor deficient mothers. Inhibiting methylation in differentiating neurons impaired their maturation further suggesting a link between de novo methylation and neuronal differentiation. These data suggest that methylation at specific exonic CpG-islands may contribute to the mechanism through which maternal 5-HT1AR modulates hippocampal development and consecutively the level of anxiety in the SW offspring. Reduced 5-HT1AR-binding has been reported in individuals, particularly in association with anxiety/depression, including peri/postpartum depression. Therefore, maternal receptor deficit may contribute, via a non-genetic mechanism, to the high prevalence and heritability of anxiety disorders in human. Overall design: Examined transcriptomes of 5HT1A wild type offspring with 5HT1A wild type/heterozygous mother or 5HT1A KO offspring with 5HT1A of heterozygous/knock out mother
Publication Title
Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 46 Downloadable Samples
- Illumina HiSeq 2000
Description
Determine allele level expression in hybrid mice of different ages Overall design: RNASeq - HybridMouseDRN
Publication Title
Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease. To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated both in primary and metastatic lesions. In an attempt to model this event, we crossed conditional activatable K-rasG12D/WT mice with the prostate conditional Pten deletion model we previously generated. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penitence. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation. Importantly, inhibition of RAS/MAPK signaling by PD325901, a MEK inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells. Collectively, these data indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis and co-targeting both pathways is highly effective in preventing the development of metastatic prostate cancers.
Publication Title
Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells.
Sample Metadata Fields
Specimen part
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