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GSE67076
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
- 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- 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- 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- Homo sapiens
- 143 Downloadable Samples
Description
We report ileal gene expression at diagnosis in a cohort of 210 treatment-naïve patients of pediatric Crohn''s disease and 35 non-IBD controls from the RISK study. After three years of follow-up after diagnosis, 27 of the CD patients progressed to complicated disease (B2 and/or B3). We aim to test whether Transcriptional Risk Scores helps to distinguish between patient subgroups, improving the predictive power gained from Genetic Risk Scores. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents (<17 years) who presented with symptoms of IBD. Non-IBD control label corresponds to those with suspected IBD, but without inflammation and normal endoscopic findings. Biopsies were stored at -80 degrees.
Publication Title
Transcriptional risk scores link GWAS to eQTLs and predict complications in Crohn's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 58 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Colon gene expression in human IBD. The three major clinical subsets of Inflammatory Bowel Disease (IBD) include colon-only Crohn's Disease (CD), ileo-colonic CD, and Ulcerative Colitis (UC). These experiments tested differential colon gene expression in these three types of IBD, relative to healthy control samples, and the local degree of mucosal inflammation as measured by the CD Histological Index of Severity (CDHIS). Colon biopsy samples were obtained from IBD patients at diagnosis and during therapy, and healthy controls. The global pattern of gene expression was determined using GeneSpring software, with a focus upon candidate genes identified in a recent genome wide association study in pediatric onset IBD. Data suggested that two of these candidate genes are up regulated in pediatric IBD, partially influenced by local mucosal inflammation.
Publication Title
Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Objective: Long non-coding RNAs (lncRNA) regulate gene transcription and diverse cellular functions. We previously defined a novel core inflammatory and metabolic ileal gene signature in treatment naïve pediatric Crohn Disease (CD), however, genome-wide characterization of lncRNA expression was lacking. We now extend our analyses to define a more comprehensive view that includes lncRNA. Design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 177 ileal biopsies. Co-expression analysis was used to identify functions and tissue-specific expression. RT-PCR was used to test lncRNAs regulation by IL-1ß in Caco-2 enterocytes model. Results: We characterize a widespread dysregulation of 459 lncRNA in the ileum of treatment naïve pediatric CD patients. Unsupervised and supervised classifications using the 459 lncRNA showed comparable patients' grouping as the 2160 dysregulated protein-coding genes, linking lncRNA to CD pathogenesis. Co-expression and functional annotation enrichment analyses across several tissues and cell types showed that the up-regulated LINC01272 is associated with a myeloid pro-inflammatory signature while the down-regulated HNF4A-AS1 exhibits association with an epithelial metabolic signature. We further validated expression and regulation of prioritized lncRNA upon IL-1ß exposure in differentiated Caco-2 cells. Finally, we identified significant correlations between LINC01272 and HNF4A-AS1 expression and more severe mucosal injury. Conclusion: We define differentially expressed lncRNA in the ileum of treatment naive pediatric CD. We show lncRNA utility to correctly classify disease or healthy states and demonstrate their regulation in response to an inflammatory signal. These lncRNA, after mechanistic exploration, may serve as potential new targets for RNA-based interventions. Overall design: Using RNAseq, we performed a systematic profiling of lncRNAs and protein-coding genes expression in 21 days differentiated caco-2 cells
Publication Title
Long ncRNA Landscape in the Ileum of Treatment-Naive Early-Onset Crohn Disease.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 172 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was isolated from rectal biopsies from 190 pediatric patients undergoing diagnostic colonoscopy for inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Single-end, 75-bp sequencing was performed, and raw reads aligned to the human genome using Gencode v 24 as reference. We included 14085 protein-coding mRNA genes in downstream analyses, where cutoffs of fold change>1.5 and FDR<0.05 were considered significant. Overall design: RNA-sequencing of rectal biopsies obtained from pediatric IBD and control patients.
Publication Title
Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- 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- 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