Filters
Technology
Platform
SRP058647
Homo sapiens
8 Downloadable Samples
IlluminaHiSeq2000
Description
Neuroblastoma cell lines can differentiate upon retinoic acid (RA) treatment, a finding that provided the basis for the clinical use of RA to treat neuroblastoma. However, resistance to RA is often observed, which limits its clinical utility. Using a gain-of-function genetic screen we identify the transcriptional coactivator Mastermind-like 3 (MAML3) as a gene whose ectopic expression confers resistance to RA. We find that MAML3 expression leads to loss of activation of a subset of RA target genes, which hampers RA-induced differentiation. The regulatory DNA elements of this subset of RA target genes show overlap in binding of MAML3 and the retinoic acid receptor, suggesting a role for MAML3 in the regulation of these genes. In addition, MAML3 has RA independent functions, including the activation of IGF1R and downstream AKT signaling via upregulation of IGF2, resulting in increased proliferation. Our results indicate an important role for MAML3 in differentiation and proliferation of neuroblastomas. Overall design: RNA-seq of SK-N-SH control and MAML3 overexpressing (SD3.23) cells, either untreated (UT) or treated with 1 µM RA (RA).
Publication Title
Mastermind-Like 3 Controls Proliferation and Differentiation in Neuroblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Physiologically, Notch signal transduction plays a pivotal role in differentiation; pathologically, Notch signaling contributes to the development of cancer. Transcriptional activation of Notch target genes involves cleavage of the Notch receptor in response to ligand binding, production of the Notch intracellular domain (NICD), and NICD migration into the nucleus and assembly of a coactivator complex. Posttranslational modifications of the NICD are important for its transcriptional activity and protein turnover. Deregulation of Notch signaling and stabilizing mutations of Notch1 have been linked to leukemia development. We found that the methyltransferase CARM1 (coactivator-associated arginine methyltransferase 1; also known as PRMT4) methylated NICD at five conserved arginine residues within the C-terminal transactivation domain. CARM1 physically and functionally interacted with the NICD-coactivator complex and was found at gene enhancers in a Notch-dependent manner. Although a methylation-defective NICD mutant was biochemically more stable, this mutant was biologically less active as measured with Notch assays in embryos of Xenopus laevis and Danio rerio. Mathematical modeling indicated that full but short and transient Notch signaling required methylation of NICD.
Publication Title
Site-specific methylation of Notch1 controls the amplitude and duration of the Notch1 response.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 299 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Initial genome sequencing and analysis of multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 299 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The MMRC reference collection is a dataset of gene expression profiling, array comparative genomic hybridization, and re-sequencing created as a resource for the Multiple Myeloma research community.
Publication Title
Initial genome sequencing and analysis of multiple myeloma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Since the discovery of induced pluripotent stem cells there has been intense interest in understanding the mechanisms that allow a somatic cell to be reprogrammed back to a pluripotent state. Several groups have studied the alterations in gene expression that occur as somatic cells modify their genome to that of an embryonic stem cell. Underpinning many of the gene expression changes are modifications to the epigenetic profile of the associated chromatin. We have used a large-scale shRNA screen to identify epigenetic modifiers that act as barriers to reprogramming. We have uncovered an important role for TRIM28 in cells resisting transition between somatic and pluripotent states. TRIM28 achieves this by maintaining the H3K9me3 repressed state and keeping endogenous retroviruses silenced. We propose that knockdown of TRIM28 during reprogramming results in more plastic H3K9me3 domains, dysregulation of genes nearby H3K9me3 marks, and up regulation of endogenous retroviruses, thus facilitating the transition through reprogramming. Overall design: Gene expression profiling using high through put sequencing at day 7 of Oct4, Sox2, Klf4 and cMyc (OSKM) expression in mouse embryonic fibroblasts with or without Trim28 / Setdb1 knockdown
Publication Title
TRIM28 is an Epigenetic Barrier to Induced Pluripotent Stem Cell Reprogramming.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
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
- 303 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this study gene expression profiles for 307 cases of advanced bladder cancers were compared to molecular phenotype at the tumor cell level. TUR-B tissue for RNA extraction was macrodissected from the close vicinity of the tissue sampled for immunohistochemistry to ensure high-quality sampling and to minimize the effects of intra-tumor heterogeneity. Despite excellent agreement between gene expression values and IHC-score at the single marker level, broad differences emerge when samples are clustered at the global mRNA versus tumor cell (IHC) levels. Classification at the different levels give different results in a systematic fashion, which implicates that analysis at both levels is required for optimal subtype-classification of bladder cancer.
Publication Title
Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
To study the senescence gene signatures in the cells, which were genetic SMARCB1 depleted or treated with aurora kinase inhibitors or etoposide, we performed next generation RNA sequencing on these cell, and ''FRIDMAN_SENESCENCE_UP'' geneset was used to determine the enrichment of senescence-related genes. The RNA sequencing results include (1) A375 cells and SMARCB1 depleted counterparts. (2) A549 cells and aurora kinase inhibitor (Alisertib, barasertib or tozasertib) or etoposide treated counterparts. Overall design: RNA seq data of A375_gSMARCB1 + A549_etoposide, Aurora kinases inhibitors treated, to check senescence gene expression signature one replicate of A375 cells parental V.S SMARCB1 KO (by CRISPR) + duplicates of A549 parental V.S etoposide, or 3 indepdent aurora kinase inhibitors (MLN8237/Alisertib, VX680/Tozasertib, AZD1132/Barasertib)
Publication Title
High-Throughput Functional Genetic and Compound Screens Identify Targets for Senescence Induction in Cancer.
Sample Metadata Fields
Disease, Disease stage, Cell line, Subject
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aging involves multiple biologically complex processes characterized by a decline in cellular homeostasis over time leading to a loss and impairment of physiological integrity and function. Specific cellular hallmarks of aging include abnormal gene expression patterns, shortened telomeres and associated biological dysfunction. Like all organs, the lung demonstrates both physiological and structural changes with age that result in a progressive decrease in lung function in healthy individuals. Cigarette smoking accelerates lung function decline over time, suggesting smoking accelerates aging of the lung. Based on this data, we hypothesized that cigarette smoking accelerates the aging of the small airway epithelium, the cells that take the initial brunt of inhaled toxins from the cigarette smoke and one of the primary sites of pathology associated with cigarette smoking. Using the sensitive molecular parameters of aging-related gene expression and telomere length, the aging process of the small airway epithelium was assessed in age matched healthy nonsmokers and healthy smokers with no physical manifestation of lung disease or abnormalities in lung function. Analysis of a 73 gene aging signature demonstrated that smoking significantly dysregulates 18 aging-related genes in the small airway epithelium. In an independent cohort of male subjects, smoking significantly reduced telomere length in the small airway epithelium of smokers by 14% compared to nonsmokers. These data provide biologic evidence that prior to the clinical manifestation of lung disease; smoking accelerates aging of the small airway epithelium.
Publication Title
Smoking accelerates aging of the small airway epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 882 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity.
Sample Metadata Fields
No sample metadata fields
View Samples