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GSE55301
Homo sapiens
4 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In order to determine BCL6 target genes an EBV negative Burkitt's lymphoma cell line, DG75, was stably transfected with a tetracycline transactivator and tight doxycycline responsive expression of GFP was established. The endogenous BCL6 genes of this cell line were disrupted by homologous recombination and a BCL6 cDNA downstream of tetracycline responsive elements (TRE) was inserted to produce Bcl6-/-:tetBCL6-HA cells. Westerns demonstrated doxycycline dependent BCL6 expression.Bcl6-/-:tet. BCL6-HA cells (clone AB7) were either grown without doxycycline (control) or with 1 ug/ml doxycycline for 16, 48 or 96 hours. Total RNA was extracted using RNeasy minipreps (Qiagen) and concentration and quality were checked on the NanoDrop ND- 1000 spectrophotometer (NanoDrop Technologies, USA) and the RNA Nano 6000 kit (Agilent Technologies) on a 2100 Bioanalyzer (Agilent Technologies). One hundred ng of total RNA was processed with the GeneChip Eukaryotic Whole Transcript Sense Target Labelling Assay kit (Affymetrix) according to the manufacturer's details. Hybridisation and scanning of GeneChips was carried out at the CSC/IC Microarray Centre, MRC Clinical Sciences Centre Imperial College London and data analysis by Bioinformatics Support Service, Imperial College London. Briefly, pre- processing of data was performed using GeneSpring GX 10.0.2 software (Agilent Technologies) which applied the "Exon RMA16" algorhithm to the data set. Exon RMA16 performs background correction, quantile normalisation, median polish summarisation and variance stabilisation of 16. In background correction, intensity values of each individual array are corrected for non-specific binding by subtracting the average signal intensity of the area between spots from each probe set. Normalisation is required so multiple chips can be compared to each other. Quantile normalisation adjusts the distribution of probe intensity of each array analysed and so that the distribution of probe intensities for each array in a set of arrays is the same. Probe summarisation refers to the conversion of probe level values (there are approximately 26 probes per gene on each GeneChip) to a single probe set expression value. Variance stabilisation of 16 refers to the addition of the value 16 to the expression values. By increasing the expression value, the variance of the data set is reduced and the distribution (defined by its mean and its variance) is stabilised.
Publication Title
Synthetic Lethal Screen Demonstrates That a JAK2 Inhibitor Suppresses a BCL6-dependent IL10RA/JAK2/STAT3 Pathway in High Grade B-cell Lymphoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Samples were taken from patients undergoing cancer excision for pagetoid (wide) sebaceous gland carcinoma (SGC) and different individuals undergoing excision for nodular (local) SGC.
Publication Title
MicroRNA and transcriptome analysis in periocular Sebaceous Gland Carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 39 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Although glucocorticoids (GCs) are known to exert numerous effects in the hippocampus, their chronic regulatory functions remain poorly understood. Moreover, evidence is inconsistent regarding the longstanding hypothesis that chronic GC exposure promotes brain aging/Alzheimer's disease. Here, we adrenalectomized male F344 rats at 15-months-of-age, maintained them for 3 months with implanted corticosterone (CORT) pellets producing low or intermediate (glucocorticoid-receptor (GR)-activating) blood levels of CORT, and performed microarray/pathway analyses in hippocampal CA1. We defined the chronic GC-dependent transcriptome as 393 genes that exhibited differential expression between Intermediate- and Low-CORT groups. Short-term CORT (4 days) did not recapitulate this transcriptome. Functional processes/pathways overrepresented by chronic CORT-upregulated genes included learning/plasticity, differentiation, glucose metabolism and cholesterol biosynthesis, whereas processes overrepresented by CORT-downregulated genes included inflammatory/immune/glial responses and extracellular structure. These profiles indicate that GCs chronically activate neuronal/metabolic processes while coordinately repressing a glial axis of reactivity/inflammation. We then compared the GC-transcriptome with a previously-defined hippocampal aging transcriptome, revealing a high proportion of common genes. Although CORT and aging moved expression of some common genes in the same-direction, the majority were shifted in opposite directions by CORT and aging (e.g., glial inflammatory genes downregulated by CORT are upregulated with aging). These results contradict the hypothesis that GCs simply promote brain aging, and also suggest that the opposite-direction shifts during aging reflect resistance to CORT regulation. Therefore, we propose a new model in which aging-related GC resistance develops in some target pathways while GC overstimulation develops in others, together generating much of the brain aging phenotype.
Publication Title
Glucocorticoid-dependent hippocampal transcriptome in male rats: pathway-specific alterations with aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study characterizes the response of primary human endothelial cells (human umbilical vein endothelial cells, HUVECs) to the relative shear stress changes that occur during the initiation of arteriogenesis at the entrance regions to a collateral artery network. HUVECs were preconditioned to a baseline level of unidirectional shear of 15 dynes/cm2 for 24 hours. After 24 hours preconditioning, HUVECs were subjected to an arteriogenic stimulus that mimics the shear stress changes observed in the opposing entrance regions into a collateral artery network. The arteriogenic stimulus consisted of a 100% step wise increase in shear stress magnitude to a unidirectional 30 dynes/cm2 in either the same or opposite direction of the preconditioned shear stress. This simulates either the feeding entrance to the collateral artery circuit or the region that drains into the vasculature downstream of an obstruction in a major artery, respectively. In vivo analysis of collateral growth in the mouse hindlimb showed enhanced outward remodeling in the re-entrant (direction reversing) region that reconnects to the downstream arterial tree, suggesting reversal of shear stress direction as a key enhancer of arteriogenesis. Transcriptional profiling using microarray techniques identified that the reversal of shear stress direction, but not an increase in shear stress alone, yielded a broad-based enhancement of the mechanotransduction pathways necessary for the induction of arteriogenesis.
Publication Title
Mechanisms of Amplified Arteriogenesis in Collateral Artery Segments Exposed to Reversed Flow Direction.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Multiple myeloma (MM) cells were treated with the BET inhibitor CPI203 alone and in combination with lenalidomide plus dexamethasone in vitro and in vivo (mouse xenograft).
Publication Title
The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in <i>in vitro</i> and <i>in vivo</i> models of multiple myeloma by blockade of Ikaros and MYC signaling.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 202 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Background: Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis.
Publication Title
The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Race
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Persistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) relates to inferior survival in multiple myeloma (MM). MRD PCs are therefore a minor clone able to recapitulate the initial tumor burden at relapse and accordingly, its characterization may represent a unique model to understand chemoresistance; unfortunately, the MRD clone has never been biologically investigated. Here, we compared the antigenic profile of MRD vs. diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study, and showed that the MRD clone is enriched by cells over-expressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4) and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs. diagnostic PCs showed identical copy number alterations (CNAs) in 3/8 cases, 2 patients with linear acquisition of additional CNAs in MRD clonal PCs, and 3 cases with variable acquisition and loss of CNAs over time. The MRD clone showed significant downregulation of genes particularly related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and identifies chemoresistant PCs in vitro. Together, we show that therapy-induced clonal selection is already present at the MRD stage, in which chemoresistant PCs show a specific phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles.
Publication Title
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 30 Downloadable Samples
Illumina HiSeq 2000
Description
We profiled total mRNA of pancreas and kidney tissues of 3 different strains (p53-null; In4a/Arf-null and WT) of reprogrammable mouse lines (they all express OCT4, SOX2, KLF4, C-MYC under the control of a tetracycline promoter, activated by doxycycline) Overall design: 5 mice of each genotype were treated with doxycycline to induce the expression of the reprogramming factors, they were sacrificed and total mRNA was extracted from pancreas and kidney tissues (we mapped >24M reads per sample)
Publication Title
Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples