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GSE21576
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To investigate the impact of ablating Bcl9/Bcl9l on tumorigenesis, 6-8- week-old mice were exposed first to a single dose dimethylhydrazine (DMH, 44 mg/kg body weight), which is metabolized in the liver to carcinogenic azoxymethane (AOM), followed by 7 days oral administration of 2 % dextrane sulfate sodium (DSS) in the drinking water. This regimen results in the emergence of dysplastic adenomas, which progress to differentiated adenocarcinomas that are morphologically similar to human colorectal adenocarcinomas and typically harbor -catenin stabilizing mutations of GSK3 phosphorylation sites. Accordingly, these tumors present hallmarks of active Wnt signaling such as accumulation of nuclear -catenin and expression of Wnt target genes.
Publication Title
Bcl9/Bcl9l are critical for Wnt-mediated regulation of stem cell traits in colon epithelium and adenocarcinomas.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Canonical Wnt signaling output is mediated by ß-catenin, which interacts with LEF/TCF transcription factors and recruits a general transcriptional activation complex to its C-terminus. Its N-terminus binds BCL9/9L proteins, which bind co-activators that in mammals contribute to fine-tuning the transcriptional output. We found that a BCL9/9L-dependent gene expression signature was strongly associated with patient outcome in colorectal cancer and that stem cell and mesenchymal genes determine its prognostic value. Abrogating BCL9/9L-ß-catenin signaling in independent mouse colorectal cancer models resulted in virtual loss of these traits, and oncogenic intestinal organoids lacking BCL9/9L proteins proved no longer tumorigenic. Our findings suggest that the BCL9/9L arm of Wnt-ß-catenin signaling sustains a stemness-to-differentiation equilibrium in colorectal cancer, which critically affects disease outcome. Mutational activation of the Wnt pathway is a key oncogenic event in colorectal cancer. Targeting the pathway downstream of activating mutations is challenging, and the therapeutic window is limited by intestinal toxicity. Contrasting with phenotypes caused by inactivating key Wnt pathway components, ablation of BCL9/9L proteins in adult mice indicated that they were dispensable for intestinal homeostasis, consistent with their role in tuning transcription. Cancer stem cells are increasingly recognized as responsible for tumor recurrence. The correlation between stemness traits in colorectal cancer models and BCL9/9L-ß-catenin signaling suggests that high Wnt signaling output is required for their maintenance. Our findings suggest that pruning Wnt-ß-catenin signaling might be well tolerated and prove sufficient for trimming stemness traits and improving disease outcome. Overall design: Examination of Bcl9/9l-knockout versus wild-type transcriptome in murine AOM-DSS tumors, APC-Kras tumors and healthy colocyte extracts.
Publication Title
BCL9/9L-β-catenin Signaling is Associated With Poor Outcome in Colorectal Cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide CpG island methylation analyses in non-small cell lung cancer patients.
Sample Metadata Fields
Specimen part, Disease, Cell line, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epigenetic changes largely contribute to the regulation of gene expression in cancer cells. DNA methylation is part of the epigenetic gene regulation complex which is relevant for the pathogenesis of cancer. We performed a genome-wide search for methylated CpG islands in tumors and corresponding non-malignant lung tissue samples of 101 stage I-III non-small cell lung cancer (NSCLC) patients by combining methylated DNA immunoprecipitation and microarray analysis using NimbleGens 385K Human CpG Island plus Promoter arrays. By testing for differences in methylation between tumors and corresponding non-malignant lung tissues, we identified 298 tumor-specifically methylated genes. From many of these genes epigenetic regulation was unknown so far. Gene Ontology analysis revealed an over-representation of genes involved in regulation of gene expression and cell adhesion. Expression of 182 of 298 genes was found to be upregulated after 5-aza-2-deoxycytidine (Aza-dC) and/or trichostatin A (TSA) treatment of 3 NSCLC cell lines by Affymetrix microarray analysis. In addition, methylation of selected genes in primary NSCLCs and corresponding non-malignant lung tissue samples were analyzed by methylation-sensitive high resolution melting analysis (MS-HRM). Our results obtained by MS-HRM analysis confirmed our data obtained by MeDIP-chip analysis. Moreover, by comparing methylation results from MeDIP-chip analysis with clinico-pathological parameters of the patients we observed methylation of HOXA2 as potential parameter for shorter disease-free survival of NSCLC patients. In conclusion, using a genome-wide approach we identified a large number of tumor-specifically methylated genes in NSCLC patients. Our results stress the importance of DNA methylation for the pathogenesis of NSCLCs.
Publication Title
Genome-wide CpG island methylation analyses in non-small cell lung cancer patients.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We demonstrate that the G protein Gi3 is the cellular target of the adenosine A3 receptor (A3R). By using a cell permeable peptide comprising the C-terminal end of Gi3 fused to an importation sequence (ALL1) as a selective inhibitor of Gi3 signaling, we show that by coupling to Gi3, the A3R stimulates multiple signaling pathways in human mast cells, leading to upregulation of cytokines, chemokines and growth factors.Following contact with activated T cell membranes, endogenous adenosine binds to and activates the A3R, resulting in Gi3-mediated signaling. Specifically, the majority of ERK1/2 signaling initiated by contact with activated T cell membranes, is mediated by Gi3, giving rise to ALL1-inhibitable cellular responses. These results unveil the physiological GPCR that couples to Gi3 and establish the important role played by this G-protein in inflammatory conditions that involve adenosine-activated mast cells.
Publication Title
Activation of mast cells by trimeric G protein Gi3; coupling to the A3 adenosine receptor directly and upon T cell contact.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 54 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We analyzed the transcriptome of dormant and after-ripened imbibed seeds of the Arabidopsis accession Cape verde Islands.
Publication Title
Dormant and after-Ripened Arabidopsis thaliana Seeds are Distinguished by Early Transcriptional Differences in the Imbibed State.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Foxp1/4 transcription factors are conserved transcriptional repressors expressed in overlapping patterns during lung development as well as in the adult lung. However, the role of Foxp1/4 in development and homeostasis of the pseudostratified epithelium of the proximal airways and trachea is unknown.
Publication Title
Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
A doxycycline-inducible system was used to induce PU.1 expression in cultured myeloid cell lines. The parent cell line used was BN (Kamath et al., Leukemia 22:1214-1225, 2008).
Publication Title
PU.1 promotes cell cycle exit in the murine myeloid lineage associated with downregulation of E2F1.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
SON is a large Ser/Arg (SR)-related protein localized in nuclear speckles. SON siRNA causes defects in mitotic progression and genome instability. We used microarrays to detail the pattern of gene expression after SON knockdown.
Publication Title
SON controls cell-cycle progression by coordinated regulation of RNA splicing.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Master regulatory genes require stable silencing by the Polycomb-Group (PcG) to prevent improper expression during differentiation and development. Some PcG proteins covalently modify histones, which contributes to heritable repression. The role for other effects on chromatin structure is less understood. We characterized the organization of PcG target genes in mouse ES cells and neural progenitors using high-resolution 5C technology and super-resolution microscopy. The genomic loci of repressed PcG target genes formed discrete, small domains of tight interaction that corresponded to locations bound by canonical Polycomb Repressive Complex 1 (PRC1). These domains changed during differentiation as PRC1 binding changed. Their formation depended upon the Polyhomeotic component of canonical PRC1, and occurred independently of PRC1-catalyzed ubiquitylation. PRC1 domains differ from topologically associating domains in numerous aspects . These domains have the potential to play a key role in transmitting epigenetic silencing of PcG targets by linking PRC1 to formation of a repressive higher order structure. Overall design: RNA-Seq was performed to compare gene expression of in vitro derived NPC and Phc1 knock-out mESC with wild type ESC. Experiments were performed in dupicates. 50base single end sequencing was performed on Illumina HiSeq2000. Reference genome is mm9.
Publication Title
Polycomb Repressive Complex 1 Generates Discrete Compacted Domains that Change during Differentiation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples