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GSE9249
Mus musculus
28 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Most human B cell lymphomas (B-NHL) are derived from germinal centers (GCs), the structure where B-cells undergo class switch recombination (CSR) and somatic hypermutation (SHM) and are selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant somatic hypermutation, which appear to arise from mistakes occurring during CSR and SHM. To ascertain the role of CSR and SHM in lymphomagenesis, we crossed three oncogene-driven (MYC, BCL6, MYC/BCL6) mouse models of B cell lymphoma with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both processes.
Publication Title
AID is required for germinal center-derived lymphomagenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 135 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adulthood, comprises multiple biologically and clinically distinct subtypes including germinal center B cell-like (GCB) and activated B cell like (ABC) DLBCL. Gene expression profile studies have shown that its most aggressive subtype, ABC-DLBCL, is associated with constitutive activation of the NF-kB transcription complex. However, except for a small fraction of cases, it remains unclear whether NF-kB activation in these tumors represents an intrinsic program of the tumor cell of origin or a pathogenetic event. Here we show that >50% of ABC-DLBCL and a smaller fraction of GCB-DLBCL carry somatic mutations at multiple genes, including negative (TNFAIP3/A20) and positive (CARD11, TRAF2, TRAF5, MAP3K7/TAK1 and TNFRSF11A/RANK) regulators of NF-kB. Of these, the A20 gene, which encodes for a ubiquitin-modifying enzyme involved in termination of NF-kB responses, is the most commonly affected one, with ~30% of the patients displaying biallelic inactivation by mutations and/or deletions, suggesting a tumor suppressor role. Less frequently, missense mutations of TRAF2 and CARD11 produce molecules with significantly enhanced ability to activate NF-kB. Thus, our results demonstrate that NF-kB activation in DLBCL is caused by genetic lesions affecting multiple genes, whose loss or activation may promote lymphomagenesis by leading to abnormally prolonged NF-kB responses.
Publication Title
Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
IlluminaHiSeq2000
Description
Chromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those generated by the ENCODE project in nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (=3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched for important cell type-specific genes; and (iii) GWAS variants associated with traits relevant to a particular cell type are more enriched in stretch enhancers compared with short enhancers. Reporter constructs containing stretch enhancer sequences exhibited tissue-specific activity in cell culture experiments and in transgenic mice. These results suggest that stretch enhancers are critical chromatin elements for coordinating cell type-specific regulatory programs and that sequence variation in stretch enhancers affects risk of major common human diseases. Overall design: Integrated analysis of islet chromatin modification and transcriptome data with those generated by the ENCODE project. NISC Comparative Sequencing Program
Publication Title
Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants.
Sample Metadata Fields
No sample metadata fields
View Samples- Oryza sativa
- 4 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Analysis of rice leaves (V2 stage) in response to a short treatment with very high CO2 concentration in the dark, using standard atmosphere as control.
Publication Title
High CO2 concentration as an inductor agent to drive production of recombinant phytotoxic antimicrobial peptides in plant biofactories.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Rattus norvegicus
- 158 Downloadable Samples
- IlluminaHiSeq2000
Description
Pineal function follows a 24-hour schedule, dedicated to the conversion of night and day into a hormonal signal, melatonin. In mammals, 24-hour changes in pineal activity are controlled by a neural pathway that includes the central circadian oscillator in the suprachiasmatic nucleus and the superior cervical ganglia (SCG), which innervate the pineal gland. In this study, we have generated the first next-generation RNA sequencing evidence of neural control of the daily changes in the pineal transcriptome. We found over 3000 pineal transcripts that are differentially expressed (p <0.001) on a night/day basis (70% of these genes increase at night, 376 with fold change >4 or <1/4), the majority of which had not been previously identified as such. Nearly all night/day differences were eliminated by neonatal removal or decentralization of the SCG, confirming the importance of neural input for differential night/day changes in transcript abundance. In contrast, very few non-rhythmic genes showed evidence of changes in expression due to the surgical procedure itself, which is consistent with the hypothesis that post neonatal neural stimulation is not required for cell fate determination and maintenance of phenotype. Many of the transcripts that exhibit marked differential night/day expression exhibited similar changes in response to in vitro treatment with norepinephrine, the SCG neurotransmitter which mediates pineal regulation. Similar changes were also seen following treatment with an analog of the norepinephrine second messenger, cyclic AMP. Overall design: For the in vivo data, there were 8 biological conditions: day and night time points for each of four surgical groups: Control (Ctrl) Sham-surgery (Sham), Decentralized (DCN), and Ganglionectomized (SCGX). Samples were pooled into three biological replicates for each biological condition. For the in vitro data there were 3 biological conditions: Untreated control (CN), DBcAMP-treated (DB), and Norepinephrine-treated (NE). For the pineal enrichment comparison, three samples (i.e. no biological replicates) were used: pineal-day, pineal-night and mixed-tissue. For the mixed tissues sample, the following tissues from three rats sacrificed at ZT7 were used: cortex, cerebellum, midbrain, hypothalamus, hindbrain, spinal cord, retina, pituitary, heart, liver, lung, kidney, skeletal muscle, small intestine, adrenal gland. Total RNA was extracted from each tissue, and then equal amounts of each of the 15 tissues were combined for the final pooled sample.
Publication Title
Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
These datasets describe a melanocyte specific, HIF1A-Dependent / Hypoxia-Responsive gene expression signature defined by the regulation of genes critical to metabolism, chromatin and transcriptional regulation, vascularization and cellular invasivness. These genes provide lineage specific targets for refinement of diagnostic markers associated with primary melanoma tumor metastatic potential, and also provides novel molecular targets for therapeutic strategies targeting metastatic disease progression.
Publication Title
Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ndn is a candidate metastasis suppressor gene that has been reported to regulate transcription.
Publication Title
Necdin is a breast cancer metastasis suppressor that regulates the transcription of c-Myc.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
We wanted to understand the consequences of GSK126-mediated Ezh2 inhibition in an orthotopic model of Kras-driven non-small cell lung cancer (NSCLC). We injected the NSCLC cells with above-mentioned genotype into Nude mice and treated them with GSK126 50mg/kg (daily) or vehicle. As additional control for Ezh2 specificity we treated one tumor with doxycycline that induces shRNA-mediated Ezh2 protein downregulation in those cells. Purified tumour cells were obtained by dissection and FACS sorting based of GFP expression. This experiment contributes the genome-wide response of NSCLC cells to Ezh2 inhibition in vivo. Overall design: We generated mRNA profiles of tumor cells tail vein injected into the lungs of Nude mice by deep sequencing. After FACS purification, RNA extraction and Bioanalyzer analysis, we processed only samples with high quality cellular and RNA profiles. Overall, we compared 10-day GSK126 treated cells (n=4) and up to 30 days GSK126 treated cells (n=3) to Captisol-treated samples (vehicle, n=2), using Illumina Hiseq2000. FACS sorted cells from individual animals were obtained by GFP expression. For H3K27ac and H2AK5ac profiling, we used KP primary tumors generated by injection of NSCLC into the tail vein of nude mice. Mice were sacrificed on the onset of shortness of breath and tissues were resuspended in ChIP lysis buffer.
Publication Title
Ezh2 inhibition in Kras-driven lung cancer amplifies inflammation and associated vulnerabilities.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Gene expression profiling of three PEL cell lines compare to three Burkitt's lymphoma lines to figure out the changed genes under KSHV latent infection.
Publication Title
The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus modulates cellular gene expression and protects lymphoid cells from p16 INK4A-induced cell cycle arrest.
Sample Metadata Fields
No sample metadata fields
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