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GSE52797
Mus musculus
7 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hearts of Myh6-MeCP2 transgenic mice and wildtype littermates were rapidly dissected and flash frozen.
Publication Title
Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure.
Sample Metadata Fields
Specimen part
View Samples- 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
- 13 Downloadable Samples
Description
Here we propose the direct conversion of human somatic cells into naive induced pluripotent cells (niPSC). Dataset: 7 expanded niPSC lines (4 from BJ cells, 1 from HFF-1, 1 from WI38, 1from IMR90), 1 freshly-isolated primary colonies of niPSC from BJ, 1 established naive embryonic line H9, 1 primed induced pluripotent cell line (from BJ), 1 sample of BJ fibroblasts, 1 sample of WI38 fibroblasts, 1 sample IMR90 fibroblasts.
Publication Title
Direct generation of human naive induced pluripotent stem cells from somatic cells in microfluidics.
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- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
We established and characterized a new recessive mutant mouse line kta41 with a point mutation in Scube3 at position 882. The mutant line was detected by screening for morphological abnormalities in the Munich ENU-mutagenesis program. The mutation was mapped by microsatellite markers to mouse chromosome 17, between markers D17MIT29 and D17MIT101. Candidate gene approaches failed due to the low recombination frequency and the high number of genes within the mapped interval. Whole genome sequencing approaches revealed a C to A transversion on position 882 in Scube3 that leads to a missense mutation in the protein (Asn294Lys). We did a broad phenotypic analysis of the mutant mouse line in the German Mouse Clinic (GMC), and followed up the found alterations by detailed phenotypic characterization. Scube3-kta41-/- mice show a series of phenotypic alterations, mainly in the skeleton, behavior and neurological abnormalities as well as changes in physiology, metabolism and immune status.
Publication Title
The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Ewing sarcoma family of tumors (ESFT) are aggressive bone and soft tissue tumors of unknown cellular origin. Most ESFT express EWS-FLI1, a chimeric protein which functions as a growth-promoting oncogene in ESFT but is toxic to most normal cells. A major difficulty in understanding EWS-FLI1 function has been the lack of an adequate model in which to study EWS-FLI1-induced transformation. Although the cell of origin of ESFT remains elusive, both mesenchymal (MSC) and neural crest (NCSC) have been implicated. We recently developed the tools to generate NCSC from human embryonic stem cells (hNCSC). In the current study we used this model to test the hypothesis that neural crest-derived stem cells are the cells of origin of ESFT and to evaluate the consequences of EWS-FLI1 expression on human neural crest biology.
Publication Title
Modeling initiation of Ewing sarcoma in human neural crest cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The full complement of molecular pathways contributing to Parkinsons disease (PD) pathogenesis remains unknown. Here, to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and -synuclein toxicity, we investigated a yeast model expressing -synuclein. Polyamines were found to enhance the toxicity of -synuclein, and an unbiased genome-wide screen for modifiers of -synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing -synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified. Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis.
Publication Title
Polyamine pathway contributes to the pathogenesis of Parkinson disease.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Drosophila melanogaster
- 58 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptome analysis may provide means to investigate the underlying genetic causes of shared and divergent phenotypes in different populations and help to identify potential targets of adaptive evolution. Applying RNA sequencing to whole male Drosophila melanogaster from the ancestral tropical African environment and a very recently colonized cold-temperate European environment at both standard laboratory conditions and following a cold shock, we seek to uncover the transcriptional basis of cold adaptation. In both the ancestral and the derived populations, the predominant characteristic of the cold shock response is the swift and massive upregulation of heat shock proteins and other chaperones. Although we find ~30% of the genome to be differentially expressed following a cold shock, only relatively few genes (n=26) are up- or down-regulated in a population-specific way. Intriguingly, 24 of these 26 genes show a greater degree of differential expression in the African population. Likewise, there is an excess of genes with particularly strong cold-induced changes in expression in Africa on a genome-wide scale. The analysis of the transcriptional cold shock response most prominently reveals an upregulation of components of a general stress response, which is conserved over many taxa and triggered by a plethora of stressors. Despite the overall response being fairly similar in both populations, there is a definite excess of genes with a strong cold-induced fold-change in Africa. This is consistent with a detrimental deregulation or an overshooting stress response. Thus, the canalization of European gene expression might be responsible for the increased cold tolerance of European flies. Overall design: mRNA profiles of whole Drosophila melanogaster adult males from a Africa (4 lines) and Europe (4 lines) during a 7h cold shock experiment. Samples include room temperature controls, 3.5h into the cold shock, 15 minutes after recovery and 90 minutes after recovery. 2 biological replicates each.
Publication Title
Canalization of gene expression is a major signature of regulatory cold adaptation in temperate Drosophila melanogaster.
Sample Metadata Fields
Sex, Subject
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Adaptively evolved mutants of yeast on galactose were characterized by feremtation physiology and tools from systems biology.
Publication Title
Unravelling evolutionary strategies of yeast for improving galactose utilization through integrated systems level analysis.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored.
Publication Title
PLZF Controls the Expression of a Limited Number of Genes Essential for NKT Cell Function.
Sample Metadata Fields
Sex, Specimen part
View Samples