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GSE26475
Mus musculus
21 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mechanical Stimuli are arguably the most important aetiolgical factors in osteoarthritis (OA) development. Not only do we see disease arising from joints where the cartilage has sustained direct (e.g. intraarticular fracture) or indirect (e.g. meniscal injury) trauma, but mechanical factors are considered, at least partly, to explain the disease associations with aging and obesity. It is now well established that OA is not simply due to repeated wear and tear, leading to attrition of the articular surfaces, but that it requires activation of a number of inflammatory genes, which drive catabolic protease activity in the joint. These enzymes lead to breakdown of the major extracellular matrix components of cartilage, namely type II collagen, and the proteoglycan, aggrecan. Although it is unclear precisely which enzymes are responsible for matrix breakdown in human OA, Glasson et al showed that deletion of the aggrecan degrading enzyme, ADAMTS5 substantially protected the joint from surgically induced murine OA suggesting that it is a major aggrecanase in the mouse.
Publication Title
Joint immobilization prevents murine osteoarthritis and reveals the highly mechanosensitive nature of protease expression in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
Illumina HiSeq 2000
Description
T4 and T5 neurons are components of the neuronal circuit for motion vision in flies. To identify genes involved in neuronal computation of T4 and T5 neurons, we perfomed transcriptome analysis. Nuclei of T4 and T5 neurons were immunoprecipitated, total RNA was harvested and used for mRNA-seq with Illumina technology. In two biological replicates, we mapped 154 and 119 million reads to D. melanogaster genome. mRNA-seq provided information about expression levels of 17,468 annotated transcripts in the T4 and T5 neurons. Overall design: Cell type – specific transcriptome analysis of the RNA isolated from immunoprecipitated nuclei, performed in two biological replicates
Publication Title
RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The activation of endothelium by tumor cells is one of the main steps by tumor metastasis. The role of the blood components (platelets and leukocytes) in this process remain unclear.
Publication Title
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
This is a large series human Duchenne muscular dystrophy patient muscle biopsies, in specific age groups, using all available Affymetrix arrays (including a custom MuscleChip produced by the Hoffman lab). Both mixed groups of patients (5 patient biopsies per group) and individual biopsies were done.
Publication Title
Expression profiling in the muscular dystrophies: identification of novel aspects of molecular pathophysiology.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
These samples were all taken from patients who underwent investigations including colonoscopy but where all tests were normal and the diagnosis of irritable bowel syndrome was reached. These observations have been used as references in studies of colonic gene expression in inflammatory bowel diseases
Publication Title
Clinical phenotype and gene expression profile in Crohn's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Elevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches, we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition.
Publication Title
Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Elevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches, we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition.
Publication Title
Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
The ubiquitous efflux transporter ATP-binding cassette sub-family C member 5 (ABCC5) is present at high levels in the blood-brain barrier, neurons and glia, but its in vivo substrates and function are not known. Untargeted metabolomic screens revealed that Abcc5-/- mice accumulate endogenous glutamate conjugates and analogs in several tissues, but brain in particular. The abundant neurotransmitter N-acetylaspartylglutamate (NAAG), for example, was over 2-fold higher in Abcc5-/- brain. In line with ABCC5-mediated transport, the metabolites that accumulated in Abcc5-/- tissues were depleted in cultured cells that overexpressed human ABCC5. Using membrane vesicles, we show that ABCC5 not only transports the metabolites detected in our screen, but also a wide range of peptides containing a C-terminal glutamate. Glutamate conjugates are of physiological relevance because they can affect the function of glutamate, the principal excitatory neurotransmitter in the brain. We found that ABCC5 also transports exogenous glutamate analogs, like the classic excitotoxic neurotoxins kainic acid, domoic acid and N-methyl-D-aspartate (NMDA) and the therapeutic glutamate analog ZJ43. Taken together, we have identified ABCC5 as a general glutamate conjugate and analog transporter that affects the disposition of endogenous metabolites, toxins and drugs. Overall design: A set of 5 wildtype brains was compared to a set of 5 Abcc5-knockout mouse brains
Publication Title
ATP-binding Cassette Subfamily C Member 5 (ABCC5) Functions as an Efflux Transporter of Glutamate Conjugates and Analogs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
HNF4alpha is a master regulator of hepatic differentiation. In this study, HNF4alpha was deleted in adult mice using a Cre-LoxP system where Cre recombinase was delivered using an AAV8 virus.
Publication Title
Hepatocyte-specific deletion of hepatocyte nuclear factor-4α in adult mice results in increased hepatocyte proliferation.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we examined the effect of T cell-derived cytokines on retinal pigment epithelial (RPE) cells with respect to expression of complement components. We used an in vitro co-culture system in which CD3/CD28-activated human T cells were separated from the human RPE cell line (ARPE-19) by a membrane. Differential gene expression in the RPE cells of complement factor genes was identified using gene arrays, and selected gene transcripts were validated by q-RT-PCR. Protein expression was determined by ELISA and immunoblotting. Co-culture with activated T cells increased RPE mRNA and/or protein expression of complement components C3, factors B, H, H-like 1, CD46, CD55, CD59, and clusterin, in a dose-dependent manner. Soluble factors derived from activated T cells are capable of increasing expression of complement components in RPE cells. This is important for the further understanding of inflammatory ocular diseases such as uveitis and age-related macular degeneration.
Publication Title
Retinal pigment epithelial cells upregulate expression of complement factors after co-culture with activated T cells.
Sample Metadata Fields
Disease, Disease stage
View Samples