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GSE6136
Mus musculus
26 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The dual bromodomain protein Brd2 is closely related to the basal transcription factor TAFII250, which is essential for cyclin A transactivation and mammalian cell cycle progression. In transgenic mice, constitutive lymphoid expression of Brd2 causes a malignancy most similar to human diffuse large B cell lymphoma. We compare the genome-wide transcriptional expression profiles of these lymphomas with those of proliferating and resting normal B cells. Transgenic tumors reproducibly show differential expression of a large number of genes important for cell cycle control and lymphocyte biology; expression patterns are either tumor-specific or proliferation-specific. Several of their human orthologs have been implicated in human lymphomagenesis. Others correlate with human disease survival time. BRD2 is underexpressed in some subtypes of human lymphoma and these subtypes display a number of similarities to the BRD2-mediated murine tumors. We illustrate with a high degree of detail that cancer is more than rampant cellular proliferation, but involves the additional transcriptional mobilization of many genes, some of them poorly characterized, which show a tumor-specific pattern of gene expression.
Publication Title
Tumor-specific and proliferation-specific gene expression typifies murine transgenic B cell lymphomagenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcriptome analysis was performed in triplicate using two human embryonic stem cells lines (hES_VUB01 and hES_SA01) by comparing the expression profiles of the undifferentiated hES cells and two types of progenitors derived from the hES cell lines: Neural progenitors (NPC) and Mesodermal progenitors (MSC).
Publication Title
Global transcriptional profiling of neural and mesenchymal progenitors derived from human embryonic stem cells reveals alternative developmental signaling pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Displacement of Bromodomain and Extra-Terminal (BET) proteins from chromatin has promise for cancer and inflammatory disease treatments, but roles of BET proteins in metabolic disease remain unexplored. Small molecule BET inhibitors, such as JQ1, block BET protein binding to acetylated lysines, but lack selectivity within the BET family (Brd2, Brd3, Brd4, Brdt), making it difficult to disentangle contributions of each family member to transcriptional and cellular outcomes. Here, we demonstrate multiple improvements in pancreatic -cells upon BET inhibition with JQ1 or BET-specific siRNAs. JQ1 (50-400 nM) increases insulin secretion from INS-1 cells in a concentration dependent manner. JQ1 increases insulin content in INS-1 cells, accounting for increased secretion, in both rat and human islets. Higher concentrations of JQ1 decrease intracellular triglyceride stores in INS-1 cells, a result of increased fatty acid oxidation. Specific inhibition of both Brd2 and Brd4 enhances insulin transcription, leading to increased insulin content. Inhibition of Brd2 alone increases fatty acid oxidation. Overlapping yet discrete roles for individual BET proteins in metabolic regulation suggest new isoform-selective BET inhibitors may be useful to treat insulin resistant/diabetic patients. Results imply that cancer and diseases of chronic inflammation or disordered metabolism are related through shared chromatin regulatory mechanisms.
Publication Title
BET Bromodomain Proteins Brd2, Brd3 and Brd4 Selectively Regulate Metabolic Pathways in the Pancreatic β-Cell.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To seek whether seasonal variation in environmental particulate matter composition affected the global gene response patterns in cultured human cells representing pulmonary and systemic vascular targets.
Publication Title
Comparative gene responses to collected ambient particles in vitro: endothelial responses.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Up to now the role of tumor-specific pTregs and anergic cells during tumor development is not fully understood. Here we used a genetically-induced tumor expressing a MHC-II restricted DBY model antigen to characterize the tumor-induced pTregs and anergic cells that arise early during tumor development.
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Up to know CD4 T cell antitumor responses have been mostly studied in transplanted tumor models. However, although they are valuable tools, they are not suitable to study the long term interactions between tumors and the immune system
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
CD4+ T cells as mediators of antitumor responses are beginning to be appreciated. Our team demonstrated that chronically activated CD4+ T cells (chCD4+ T cells) were expanded in the blood of cancer patients and their expansion is correlated with tumor regression.
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 6 Downloadable Samples
NextSeq 500
Description
RNA-SEQ of mutants B cell for IgH 3''RR and Emu Overall design: CD43- splenic B-cells from wt, Eµ-deficient or 3''RR deficient mice, non stimulated (NS) or stimulated (S) with 5mg/ml LPS.
Publication Title
E<sub>μ</sub> and 3'RR IgH enhancers show hierarchic unilateral dependence in mature B-cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
VAF347 is a low molecular weight compound which inhibits allergic lung inflammation in vivo. This effect is likely due to a block of dendritic cell (DC) function to generate pro-inflammatory T-helper (Th) cells since VAF347 inhibits IL-6, CD86 and HLA-DR expression by human monocyte derived DC, three relevant molecules for Th-cell generation. Here we demonstrate that VAF347 interacts with the aryl hydrocarbon receptor (AhR) protein resulting in activation of the AhR signaling pathway. Functional AhR is responsible for the biological activity of VAF347 since, i) other AhR agonists display an identical activity profile in vitro, ii) gene silencing of wild type AhR expression or forced over-expression of a trans-dominant negative AhR ablates VAF347 activity to inhibit cytokine induced IL-6 expression in a human monocytic cell line and iii) AhR deficient mice are resistant to the compounds ability to block allergic lung inflammation in vivo. These data identify the AhR protein as key molecular target of VAF347 and its essential role for mediating the anti-inflammatory effects of the compound in vitro and in vivo.
Publication Title
Activation of the aryl hydrocarbon receptor is essential for mediating the anti-inflammatory effects of a novel low-molecular-weight compound.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq 500
Description
The IgH 3' regulatory region (3'RR) controls class switch recombination (CSR) and somatic hypermutation (SHM) in B cells. The mouse 3'RR contains four enhancer elements with hs1,2 flanked by inverted repeated sequences and the center of a 25-kb palindrome bounded by two hs3 enhancer inverted copies (hs3a and hs3b). hs4 lies downstream of the palindrome. Evolution maintained in mammals this unique palindromic arrangement suggesting that it is functionally significant. We report that deconstructing the palindromic IgH 3'RR strongly impacts its function even when enhancers are preserved. CSR and IgH transcription appear poorly dependent from the 3'RR architecture and are more or less preserved provided 3'RR enhancers are present. By contrast, an “architectural effect” significantly lowers VH germline transcription, AID recruitment and SHM. In conclusion, this work indicates that the IgH 3'RR does not simply pile up enhancer units but also optimally expose them into a functional architecture of crucial importance. Overall design: RNAseq analysis of B-cell splenocytes with (S=stimulated) or without (R=resting) LPS activation from wt, delta2leftPAL, and deltaIRIS mice.
Publication Title
Deciphering the importance of the palindromic architecture of the immunoglobulin heavy-chain 3' regulatory region.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples