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GSE81245
Mus musculus
24 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Spinal muscular atrophy (SMA) is a neurodegenerative disease which exhibits selective motor neuron death caused by a ubiquitous deficiency of the survival motor neuron (SMN) protein. It remains unclear how the ubiquitous reduction of SMN lead to death in selective motor neuron pools. Medial motor neuron columns (MMC) are vulnerable, whereas lateral motor columns (LMC) are resistant to motor neuron death in SMA. Here we performed microarray and pathway analysis comparing cholera toxin subunit B (CTb) labeled vulnerable MMC and resistant LMC of pre-symptomatic SMA with corresponding motor neuron columns of control mice to identify pathways involved in selective motor neuron death in SMA. WT is FVB. SMN is Delta7 (SMN7;SMN2;Smn-) on a FVB background.
Publication Title
Converging Mechanisms of p53 Activation Drive Motor Neuron Degeneration in Spinal Muscular Atrophy.
Sample Metadata Fields
Specimen part
View Samples- Sus scrofa
- 29 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
The age groups were used to investigate how gene expression differences between the brachial and the femoral artery effect the heterogeneous atherosclerotic disease initiation and progression.
Publication Title
Gene expression differences in healthy brachial and femoral arteries of Rapacz familial hypercholesterolemic swine.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarray analyses of patient myeloma cells (n=52) to correlate individual miRNA expression profiles with GEP-based risk defined by mRNA expression profilesx as well as clinical features of the disease. Unlike for mRNAs, genome-wide elevation of miRNA expression patterns were significantly positively associated with a mRNA-based GEP-risk score (P <.01) and proliferation index (P <.05). Consistent with our observation of global deregulation of miRNA expression profiles, silencing EIF2C2/AGO2, a gene component of the mRNA-based high-risk signature and a master regulator of the genesis and functionality of all miRNAs, dramatically decreased viability in myeloma cell lines.
Publication Title
High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 130 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Purpose: Because dexamethasone remains a key component of myeloma therapy, we wished to examine the correlation of baseline and relapse expression levels of the glucocorticoid receptor gene NR3C1 with other clinical features. Experimental Design: We investigated the clinical impact of gene expression profiling (GEP)derived expression levels of NR3C1 in 351 patients with GEP data available at baseline and in 130 with data available at relapse, among 668 subjects accrued to Total Therapy 2 (TT2).
Publication Title
Thalidomide in total therapy 2 overcomes inferior prognosis of myeloma with low expression of the glucocorticoid receptor gene NR3C1.
Sample Metadata Fields
Disease, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Obesity induces macrophages to drive inflammation in adipose tissue, a crucial step towards the development of type 2 diabetes. The tricarboxylic acid (TCA) cycle intermediate succinate is released from cells under metabolic stress and has recently emerged as a metabolic signal induced by proinflammatory stimuli. We therefore investigated whether succinate receptor 1 (SUCNR1) could play a role in the development of adipose tissue inflammation and type 2 diabetes. Succinate levels were determined in human plasma samples from individuals with type 2 diabetes and non-diabetic participants. Succinate release from adipose tissue explants was studied. Sucnr1 -/- and wild-type (WT) littermate mice were fed a high-fat diet (HFD) or low-fat diet (LFD) for 16 weeks. Serum metabolic variables, adipose tissue inflammation, macrophage migration and glucose tolerance were determined. We show that hypoxia and hyperglycaemia independently drive the release of succinate from mouse adipose tissue (17-fold and up to 18-fold, respectively) and that plasma levels of succinate were higher in participants with type 2 diabetes compared with non-diabetic individuals (+53%; p < 0.01). Sucnr1 -/- mice had significantly reduced numbers of macrophages (0.56 0.07 vs 0.92 0.15 F4/80 cells/adipocytes, p < 0.05) and crown-like structures (0.06 0.02 vs 0.14 0.02, CLS/adipocytes p < 0.01) in adipose tissue and significantly improved glucose tolerance (p < 0.001) compared with WT mice fed an HFD, despite similarly increased body weights. Consistently, macrophages from Sucnr1 -/- mice showed reduced chemotaxis towards medium collected from apoptotic and hypoxic adipocytes (-59%; p < 0.05). Our results reveal that activation of SUCNR1 in macrophages is important for both infiltration and inflammation of adipose tissue in obesity, and suggest that SUCNR1 is a promising therapeutic target in obesity-induced type 2 diabetes.
Publication Title
SUCNR1-mediated chemotaxis of macrophages aggravates obesity-induced inflammation and diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 147 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Molecular and genomic analysis of microscopic quantities of tumor from formalin-fixed and paraffin-embedded (FFPE) biopsies has many unique challenges. Here we evaluated the feasibility of obtaining transcriptome-wide RNA expression to measure prognostic classifiers from diagnostic prostate needle core biopsies.
Publication Title
Application of a Clinical Whole-Transcriptome Assay for Staging and Prognosis of Prostate Cancer Diagnosed in Needle Core Biopsy Specimens.
Sample Metadata Fields
Specimen part, Subject
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Gene 1.0 ST Array (elegene10st)
Description
The excessive perchlorate utilization as an oxidizer in rocket propellants and blasting agents had led to the contamination of surface and ground waters. This chemical is known to compete with iodine for binding to the thyroid membrane receptors potentially causing hypothyroidism and fetal retardation in pregnant women. Nevertheless, to date, its biological effects are not completely understood. We have investigated the molecular mechanisms responsive to perchlorate in the nematode C. elegans to nominate a candidate gene for further peruse in the development of a C.elegans perchlorate biosensor. Perchlorate (1 mg/mL) affected the transcriptional response of Regulation of developmental process, growth, defense mechanisms and stress response, among other biological processes.
Publication Title
Perchlorate detection <i>via</i> an invertebrate biosensor.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Genes upregulated by low oxygen have been suggested as endogenous markers for tumor hypoxia. Yet, most of the genes investigated have shown inconsistent results, which have led to concerns about their ability to be true hypoxia markers. Previous studies have demonstrated that expression of hypoxia induced genes can be affected by extracellular pH (pH e ). Methods: Five different human cell lines (SiHa, FaDu DD, UTSCC5, UTSCC14 and UTSCC15) were exposed to different oxygen concentrations and pH (7.5 or 6.3), and gene expression analyzed with microarray (Affymetrix - Human Genome U133 Plus 2.0 Array). Results: An analysis of two of the cell lines using SAM identified 461 probesets that were able to separate the four groups Normal oxygen, normal pH , Low oxygen, normal pH , Normal oxygen, low pH and Low oxygen, low pH . From here it was possible to identify a fraction of probesets induced at low oxygen independent of pH in these two cell lines, this fraction included HIG2, NDRG1, PAI1 and RORA. Further verifi cation by qPCR highlighted the necessity of using more cell lines to obtain a robust gene expression profi les. To specifi cally select pH independent hypoxia regulated genes across more cell lines, data for FaDu DD, UTSCC5, UTSCC14 and UTSCC15 were analyzed to identify genes that were induced by hypoxia in each cell line, where the induction was not affected by low pH, and where the gene was not signifi cantly induced by low pH alone. Each cell line had 65 122 probesets meeting these criteria. For genes to be considered as target genes (hypoxia inducible pH independent), genes had to be present in three of four cell lines. Conclusion: The result is a robust hypoxia profile unaffected by pH across cell lines consisting of 27 genes. This study demonstrates a way to identify hypoxia markers by microarray, where other factors in the tumor microenvironment are taken into account.
Publication Title
Identifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 5 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Altered patterns of transcription factor (TF) binding are now accepted as a hallmark of many aggressive cancers including prostate and breast cancers1,2. This implies that underlying global changes in chromatin accessibility may drive cancer progression, as previously hypothesized3-5. In addition there are epigenetic readers such as bromodomain containing protein 4 (BRD4), which have been shown to associate with these TFs6-8 and also to contribute to aggressive cancers of many types8,9 including prostate cancer (PC)6,10. Here we show for the first time that formaldehyde-assisted isolation of regulatory elements followed by sequencing (FAIRE-seq) applied to human prostate tumors tissue can define castrate-resistant prostate cancer (CRPC) and can be used to inform the discovery of gene-level classifiers for therapy. In addition, we show that the androgen receptor (AR) overexpression alone is a primary driver for chromatin relaxation and that this effect can be reversed using bromodomain inhibitors. We also report that bromodomain-containing proteins (BRDs) are overexpressed in advanced CRPCs and that ATAD2 and BRD2 have prognostic value. In conclusion, this is the first study demonstrating a major impact of BRDs on chromatin accessibility in CRPC in patient samples. Consequently, targeting bromodomains provides a compelling rational for combination therapy in which BRD-mediated TF binding is enhanced or modified as cancer progresses.
Publication Title
Androgen Receptor Deregulation Drives Bromodomain-Mediated Chromatin Alterations in Prostate Cancer.
Sample Metadata Fields
Time
View Samples