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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- Danio rerio
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
Compared to other fish models, miRNAs are currently most extensively studied and identified in zebrafish. Approximately 415 dre-miRNAs have been identified and several articles have studied some aspect of miRNA function in zebrafish such as their role in basic development and in disease pathways. However, this field of research is in its infancy and the function of several dre-miRNAs, as well as their tissue-specific expression profile, are yet to be defined. In this study, the liver and gut were dissected (wildtype/untreated fish), total and small RNA were extracted, mRNA and miRNA libraries constructed and subjected to high throughput sequencing (HTS) using standard approaches. We carried out differential expression (DE) analysis and compared liver miRNA expression to gut using established bioinformatics pipelines. Through bioinformatics analysis, known and putative novel miRNAs were identified. Finally, we constructed a “miRNA matrix” that connects both total RNA-Seq and miRNA-Seq. Overall design: Examination of transcriptome in an in vivo model organism in two defined tissues, liver and gut.
Publication Title
Interplay Between MicroRNAs and Targeted Genes in Cellular Homeostasis of Adult Zebrafish (<i>Danio rerio</i>).
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Homo sapiens
- 202 Downloadable Samples
Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 202 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
Gene expression analyses in whole blood reveal a network of genes related to schizophrenia
Publication Title
A gene co-expression network in whole blood of schizophrenia patients is independent of antipsychotic-use and enriched for brain-expressed genes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
HCT116 colon carcinoma cells invade more the basement membrane when carcinoma-associated fibroblasts (CAFs) are present. In order to identify if CAFs induce an invasive phenotype to HCT116 cells, and therefore regulate genes expression related to invasion, we compared gene expression of HCT116 cells cultured alone or in the presence of CAFs.
Publication Title
Cancer-associated fibroblasts induce metalloprotease-independent cancer cell invasion of the basement membrane.
Sample Metadata Fields
Disease, Cell line
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genes responses in A549 and H460 cells after GSI (RO4929097-001-003 , 2 uM) treatment.
Publication Title
Preclinical profile of a potent gamma-secretase inhibitor targeting notch signaling with in vivo efficacy and pharmacodynamic properties.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina human-6 v2.0 expression beadchip
Description
PRC, a member of the PGC-1 coactivator family, is responsive to serum growth factors and up regulated in proliferating cells. Here, we investigated its in vivo role by stably silencing PRC expression with two different short hairpin RNAs (shRNA#1 and shRNA#4) that were lentivirally introduced into U2OS cells. ShRNA#1 transductants exhibited nearly complete knockdown of PRC protein whereas shRNA#4 transductants expressed PRC protein at approximately 15 percent of the control level. Complete PRC silencing by shRNA#1 resulted in a severe inhibition of respiratory growth, reduced expression of respiratory protein subunits from complexes I, II, III and IV, markedly lower complex I and IV respiratory enzyme levels and diminished mitochondrial ATP production. Surprisingly, shRNA#1 transductants exhibited a striking proliferation of abnormal mitochondria that were devoid of organized cristae and displayed severe membrane abnormalities. Although shRNA#4 transductants had normal respiratory subunit expression and a moderately diminished respiratory growth rate, both transductants showed markedly reduced growth on glucose accompanied by inhibition of G1/S cell cycle progression. Microarray analysis revealed striking overlaps in the genes affected by PRC silencing in the two transductants and the functional identities of these overlapping genes were consistent with the observed mitochondrial and cell growth phenotypes. The consistency between phenotype and PRC expression levels in the two independent transductant lines argues that the defects result from PRC silencing and not from off target effects. These results support a role for PRC in the integration of pathways directing mitochondrial respiratory function and cell growth.
Publication Title
Short hairpin RNA-mediated silencing of PRC (PGC-1-related coactivator) results in a severe respiratory chain deficiency associated with the proliferation of aberrant mitochondria.
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- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human blood monocytes were differentiated over six days with either 100 ng/ml M-CSF or 1 umol/l CXCL4
Publication Title
CXC chemokine ligand 4 induces a unique transcriptome in monocyte-derived macrophages.
Sample Metadata Fields
Specimen part
View Samples