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GSE4356
Mus musculus
27 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Deregulated expression of the Myc transcription factor is a frequent causal mutation in human cancer. Thousands of putative Myc target genes have been identified in in vitro studies, indicating that Myc exerts highly pleiotropic effects within cells and tissues. However, the complexity and diversity of Myc gene targets has confounded attempts at identifying which of these genes are the critical targets mediating Myc-driven tumorigenesis in vivo. Acute activation of Myc in a reversibly switchable transgenic model of Myc-mediated cell tumorigenesis induces rapid tumor onset whereas subsequent Myc de-activation triggers equally rapid tumor regression. Thus, sustained Myc activity is required for tumor maintenance. We have used this reversibly switchable kinetic tumor model in combination with high-density oligonucleotide microarrays to develop an unbiased strategy for identifying candidate Myc-regulated genes responsible for maintenance of Myc-dependent tumors. Consistent with known Myc functions, some Myc-regulated genes are involved in cell growth, cycle and proliferation. In addition, however, many Myc-regulated genes are specific to cells, indicating that a significant component of Myc action is cell-type specific. Finally, we identify a very restricted cadre of genes whose expression is inversely regulated upon Myc activation-induced tumor progression and de-activation-induced tumor regression. By definition, such genes are candidates for tumor maintenance functions. Combining reversibly switchable, transgenic models of tumor formation and regression with genomic profiling offers a novel strategy with which to deconvolute the complexities of oncogenic signaling pathways in vivo
Publication Title
Reversible kinetic analysis of Myc targets in vivo provides novel insights into Myc-mediated tumorigenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 2 Downloadable Samples
NextSeq 500
Description
Znf536 mutant and wild types were profiled to discover cell type landscape modulated by the transcription factor. Overall design: 10x libraries of single cell transcriptomes
Publication Title
Phenotypic Landscape of Schizophrenia-Associated Genes Defines Candidates and Their Shared Functions.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2000
Description
Small ubiquitin-like modifier (SUMO) family proteins regulate target protein functions by post-translational modification. However, a potent and selective inhibitor to target the SUMO pathway has been lacking. Here we describe ML-792, the first mechanism-based SUMO-activating enzyme (SAE) inhibitor with nanomolar potency in cellular assays. ML-792 selectively blocks SAE enzyme activity and total SUMOylation, which leads to reduced cancer cell proliferation. Moreover, induction of the MYC oncogene increased the ML-792 mediated viability effect in cancer cells, indicating potential application of SAE inhibitors in MYC-amplified tumors. Using ML-792, we further explored the critical roles of SUMOylation in mitotic progression and chromosome segregation. Furthermore, expression of an SAE catalytic subunit (UBA2) mutant S95N/M97T rescued SUMOylation loss and the mitotic defect induced by ML-792, confirming the selectivity of ML-792. As a potent and selective SAE inhibitor, ML-792 provides rapid loss of endogenously SUMOylated proteins allowing for novel insights into SUMO biology. Overall design: RNA-SEQ was used to analyze changes in mRNA profiles of human colon and breast cancer cells treated with ML00754792 SAEi
Publication Title
Probing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Homo sapiens
- 171 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The behavior of breast cancers and their response to different chemotherapy treatments depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Publication Title
Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer.
Sample Metadata Fields
Age, Race
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 4000
Description
The overall aim of this experiment was to identify specific genes and molecular pathways regulated by ML290, a small molecule agonist of the relaxin receptor, RXFP1, in the context of liver fibrosis. Overall design: Whole transcriptome mRNA sequencing of transformed LX-2 cells using HiSeq platforms with paired-end 150 bp (PE 150) sequencing strategy, with four biological replicates in each treatment group.
Publication Title
Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
One of the major players controlling RNA decay is the cytoplasmic 5'-to-3' exoribonuclease, which is conserved among eukaryotic organisms. In Arabidopsis, the 5'-to-3' exoribonuclease XRN4 is involved in disease resistance, the response to ethylene, RNAi, and miRNA-mediated RNA decay. Curiously, XRN4 appears to display selectivity among its substrates because certain 3' cleavage products formed by miRNA-mediated decay, such as from ARF10 mRNA, accumulate in the xrn4 mutant, whereas others, such as from AGO1, do not. To examine the nature of this selectivity, transcripts that differentially accumulate in xrn4 were identified by combining PARE and Affymetrix arrays. Certain functional categories, such as stamen-associated proteins and hydrolases, were over-represented among transcripts decreased in xrn4, whereas transcripts encoding nuclear-encoded chloroplast-targeted proteins and nucleic acid-binding proteins were over-represented in transcripts increased in xrn4. To ascertain if RNA sequence influences the apparent XRN4 selectivity, a series of chimeric constructs was generated in which the miRNA-complementary sites and different portions of the surrounding sequences from AGO1 and ARF10 were interchanged. Analysis of the resulting transgenic plants revealed that the presence of a 150 nucleotide sequence downstream from the ARF10 miRNA-complementary site conferred strong accumulation of the 3' cleavage products in xrn4. In addition, sequence analysis of differentially accumulating transcripts led to the identification of 27 hexamer motifs that were over-represented in transcripts or miRNA-cleavage products accumulating in xrn4. Taken together, the data indicate that specific mRNA sequences, like those in ARF10, and mRNAs from select functional categories are attractive targets for XRN4-mediated decay.
Publication Title
Evidence that XRN4, an Arabidopsis homolog of exoribonuclease XRN1, preferentially impacts transcripts with certain sequences or in particular functional categories.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 320 Downloadable Samples
- NextSeq 500
Description
Certain neuron types fire spontaneously at high rates, an ability that is crucial for their function in brain circuits. The spontaneously active GABAergic neurons of the substantia nigra pars reticulata (SNr), a major output of the basal ganglia, provide tonic inhibition of downstream brain areas. A depolarizing "leak" current supports this firing pattern, but its molecular basis remains poorly understood. To understand how SNr neurons maintain tonic activity, we used single-cell RNA sequencing to determine the transcriptome of individual SNr neurons. We discovered that SNr neurons express the sodium leak current, NaLCN and that SNr neurons lacking NaLCN have impaired spontaneous firing. Overall design: RNA sequencing profiles from 87 GFP-positive GABAergic SNr neurons and 9 GFP-negative SNr cells were carried out. However only 80 samples that passed initial quality control and that were included in the data processing are represented in this record.
Publication Title
The leak channel NALCN controls tonic firing and glycolytic sensitivity of substantia nigra pars reticulata neurons.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of artifactual microarray probe signals constantly present in multiple sample types.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The correlation of the RNA profiles obtained by microarray analysis was compared with that obtained from RNA-Seq by using reduced complexity sperm datasets. This resolved as a series of discordant probes. The extent of discordancy among other datasets was then determined.
Publication Title
Identification of artifactual microarray probe signals constantly present in multiple sample types.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Transcriptome analysis of depletion of DYRK1A in HeLa cells
Publication Title
DYRK1A phoshorylates histone H3 to differentially regulate the binding of HP1 isoforms and antagonize HP1-mediated transcriptional repression.
Sample Metadata Fields
Specimen part, Cell line
View Samples