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GSE24473
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
RASSF1C, unlike RASSF1A, is not a tumor suppressor, but instead may play a role in stimulating metastasis and survival in breast cancer cells
Publication Title
Ras-association domain family 1C protein promotes breast cancer cell migration and attenuates apoptosis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Dissection of melanoma heterogeneity through gene expression profiling has led to the identification of two major phenotypes, conventionally defined as MITF high / proliferative and AXL high / invasive. Tumors or single melanoma cells characterized by a predominant AXL-related gene program show enhanced expression of sets of genes involved in motility, invasion and regulation of epithelial-mesenchymal transition (EMT), while these genes are downregulated in tumors or cells with a predominant MITF-related gene program. The activation of the AXLhi/MITFlo invasive gene program in melanoma is characterized by aberrant expression of transcription factors (TFs) involved in the embryonic EMT process. Additional master genes involved in promoting melanoma growth and invasive state have been identified within the family of epigenetic regulators. Two of these genes, RNF2 and EZH2, components of the polycomb repressive complexes 1 and 2, act by epigenetically silencing tumor suppressors that in turn regulate the invasive and EMT-like phenotype of melanoma cells. Additional master genes involved in promoting melanoma growth and invasive state have been identified within the family of epigenetic regulators. Two of these genes, RNF2 and EZH2, components of the polycomb repressive complexes 1 and 2, act by epigenetically silencing tumor suppressors that in turn regulate the invasive and EMT-like phenotype of melanoma cells. Here we provide evidence for a new actionable pathway that controls melanoma EMT-like/invasive phenotype. We show that in MITFlo melanomas, the TF NFATc2 controls the EMT-like transcriptional program, the invasive ability of neoplastic cells, as well as in-vitro and in-vivo growth, through a pathway that functionally links c-myc to FOXM1 and EZH2. Targeting of NFATc2, FOXM1 or EZH2 inhibited melanoma migratory and invasive activity. Moreover, pharmacological co-targeting of NFATc2 and EZH2 promoted apoptosis of BRAF-mutant melanomas with intrinsic resistance to BRAF inhibition.
Publication Title
An actionable axis linking NFATc2 to EZH2 controls the EMT-like program of melanoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
Illumina HiSeq 2000
Description
We report the transcriptome changes that result of the genomic deletion of one or two alleles of an islet-specific long non-coding RNA (Blinc1) in isolated pancreas from e15.5 mouse embryos. Overall design: Pancreas from e15.5 embryos were dissected and total RNA extracted. Libraries were prepared from total RNA (RIN>8) with the TruSeq RNA prep kit (Illumina) and sequenced using the HiSeq2000 (Illumina) instrument. More than 20 million reads were mapped to the mouse genome (UCSC/mm9) using Tophat (version 2.0.4) with 4 mismatches and 10 maximum multiple hits. Significantly differentially expressed genes were calculated using DEseq.
Publication Title
βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Therapeutic targeting of BRAFV600Eand of MEK has shown a significant impact on progression-free and overall survival in advanced melanoma, but only a fraction of patients benefit from these treatments, suggesting that additional signaling pathways involved in melanoma growth/survival need to be identified. To this end, we used whole genome microarray analysis to identify differentially expressed genes in a set of neoplastic clones, isolated from a single melanoma metastasis, and characterized by mututally exclusive expression of BRAFV600E or NRASQ61R. By this approach we identified two genes, SEMA6A and Mical-1 belonging to the semaphorin-plexin signaling pathway and higly expressed, at mRNA and protein level, in BRAF-mutant neoplastic clones. Real-time PCR, Western blot analysis and immunohistochemistry confirmed the preferential expression of SEMA-6A and Mical-1 in BRAFV600E neoplastic cells from melanoma clones, primary and metastatic cell lines and tissue sections from melanoma lesions. SEMA6A depletion, by specific RNA-interference experiments, led to cytoskeletal remodeling, loss of stress fibers, generation of actin-rich protrusion, and cell death, whereas SEMA6A overexpression, in NRASQ61R clones, promoted invasiveness. Mical-1 depletion, by siRNA, in BRAFV600E melanomas, did not alter the actin cytoskeleton organization but caused a strong NDR phosphorylation and NDR-dependent apoptosis. Overall, these results suggest that the SEMA and MICAL pathways contribute to promote survival of BRAFV600E melanomas.
Publication Title
Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
CCR6+ innate lymphoid cells were sorted from the mesenteric lymph node of nave C57BL/6 mice
Publication Title
Immune tolerance. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4⁺ T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Aim: Transcriptional analysis of the duodenum of adult Nkx2.2flox/SD;Villin-Cre (SDint) mice versus control Methods: 2 cm of the duodenum (as measured from the stomach) of 6 week old control and mutant mice were dissected and total RNA extracted. Libraries were prepared from total RNA (RIN>8) with the TruSeq RNA prep kit (Illumina) and sequenced using the HiSeq2000 (Illumina) instrument. More than 20 million reads were mapped to the mouse genome (UCSC/mm9) using Tophat (version 2.0.4) with 4 mismatches and 10 maximum multiple hits. Significantly differentially expressed genes were calculated using DEseq. Results: 206 genes with a p-value <0.05 were significantly changed. Among these are some enteroendocrine hormones. Conclusion: The SD domain of Nkx2.2 regulates specification of some enteroendocrine cells Overall design: mRNA profiles of the duodenum of 6 week old control and SDint mice were generated by deep sequencing, in triplicate, using Illumina HiSeq2000.
Publication Title
The novel enterochromaffin marker Lmx1a regulates serotonin biosynthesis in enteroendocrine cell lineages downstream of Nkx2.2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Aim: Transcriptional analysis of the colon of adult Nkx2.2flox/flox;Villin-Cre (Nkx2.2int) mice versus control Methods: 2 cm of the colon (as measured after the caecum) of 6 week old control and mutant mice were dissected and total RNA extracted. Libraries were prepared from total RNA (RIN>8) with the TruSeq RNA prep kit (Illumina) and sequenced using the HiSeq2000 (Illumina) instrument. More than 20 million reads were mapped to the mouse genome (UCSC/mm9) using Tophat (version 2.0.4) with 4 mismatches and 10 maximum multiple hits. Significantly differentially expressed genes were calculated using DEseq. Results: 53 genes with a p-value <0.05 were down-regulated and 36 were up-regulated. Among the changed genes are enteroendocrine hormones. Conclusion: Nkx2.2 regulates enteroendocrine cell specification Overall design: mRNA profiles of the colon of 6 week old control and Nkx2.2int mice were generated by deep sequencing, using Illumina HiSeq2000.
Publication Title
The novel enterochromaffin marker Lmx1a regulates serotonin biosynthesis in enteroendocrine cell lineages downstream of Nkx2.2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
Interleukin (IL)-2 is a pleiotropic cytokine that is necessary to prevent chronic inflammation in the gastrointestinal tract. The protective effects of IL-2 involve the generation, maintenance and function of regulatory T cells (Tregs), and low-dose IL-2 has emerged as a potential therapeutic strategy in inflammatory bowel disease (IBD) patients. However, the cellular and molecular pathways that control the production of IL-2 in the context of intestinal health are undefined. Here we identify that IL-2 is acutely required to maintain Tregs and immunologic homeostasis throughout the gastrointestinal tract. Strikingly, lineage-specific deletion of IL-2 in T cells could recapitulate these phenotypes in the large intestine, but not in the small intestine. Unbiased analyses revealed that group 3 innate lymphoid cells (ILC3) are the dominant cellular source of IL-2 in the small intestine, which is selectively induced by IL-1ß. Macrophages produce IL-1ß in the small intestine and activation of this pathway involves MyD88- and Nod2-dependent sensing of the microbiota. Loss-of-function studies defined that ILC3-derived IL-2 is essential to maintain Tregs, immunologic homeostasis and oral tolerance to dietary antigens uniquely in the small intestine. Furthermore, ILC3 production of IL-2 was significantly reduced in the small intestine of Crohn's disease patients, and this correlated with diminished Tregs. Collectively, these results reveal a previously unappreciated pathway whereby a microbiota- and IL-1ß-dependent axis promotes ILC3 production of IL-2 to orchestrate immune regulation in the small intestine. Overall design: RNAs of ILC3s or CD4+ T cells were respectively sorted as CD45+CD3-ROR?tGFP+CD127+ or CD45+CD3+CD4+ from 3 wild type mice.
Publication Title
Innate lymphoid cells support regulatory T cells in the intestine through interleukin-2.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The aim of this analysis was to investigate the changes in the gene expression pattern of ex vivo cultured wildtype murine osteoclasts during the course of osteoclastogenic differentiation.
Publication Title
The Lysosomal Protein Arylsulfatase B Is a Key Enzyme Involved in Skeletal Turnover.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This study was aimed at identifying Tbx1 dosage-dependent genes in vivo, so we performed a transcriptome analysis of Tbx1 mutants with nine different genotypes corresponding to different Tbx1 mRNA dosages.
Publication Title
In vivo response to high-resolution variation of Tbx1 mRNA dosage.
Sample Metadata Fields
Specimen part
View Samples