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GSE14406
Mus musculus
53 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Inadequate remyelination of brain white matter lesions has been associated with a failure of oligodendrocyte precursors to differentiate into mature, myelin-producing cells. In order to better understand which genes play a specific role in oligodendrocyte differentiation we performed time dependent, genome-wide gene expression studies of mouse Oli-neu cells as they differentiate into myelin basic protein-producing cells, following treatment with three different agents. Our data indicate that different inducers activate distinct pathways that ultimately converge into the differentiated state where regulated gene sets overlap maximally.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 294 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancer, a leading cause of cancer related deaths, is a heterogeneous disease, with little consensus on molecular subclasses and their clinical relevance. We describe four molecular subtypes linked with distinct patterns of molecular alterations, disease progression and prognosis viz. a) Microsatellite Instable: hypermutated intestinal subtype tumors occurring in antrum, best overall prognosis, lower frequency of recurrence (22%), with liver metastasis in 23% of recurred cases b) Mesenchymal-like: diffuse tumors with worst prognosis, a tendency to occur at an earlier age and highest recurrence (63%) with peritoneal seeding in 64% of recurred cases, low frequency of molecular alterations c) TP53-inactive with TP53 loss, presence of focal amplifications and chromosomal instability d) TP53-active marked by EBV infection and PIK3CA mutations. The key molecular mechanisms and associated survival patterns are validated in multiple independent cohorts, to provide a consistent and unified framework for further preclinical and clinical research.
Publication Title
Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 294 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 66 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gastric cancers with mismatch repair (MMR) inactivation are characterised by microsatellite instability (MSI). In this study, the transcriptional profile of 38 gastric cancers with and without MSI was analysed.
Publication Title
Genome-wide expression profile of sporadic gastric cancers with microsatellite instability.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Objective. To identify novel monosodium urate (MSU) crystal-induced mRNAs by transcript profiling of isolated murine air pouch membranes.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic ductal adenocarcinoma (PDAC) is a nearly uniformly lethal malignancy, with most patients facing an adverse clinical outcome. Given the pivotal role of aberrant Notch signaling in the initiation and progression of PDAC, we investigated the effect of MRK-003, a potent and selective -secretase inhibitor, in preclinical PDAC models. We used a panel of human PDAC cell lines, as well as patient-derived PDAC xenografts, to determine whether pharmacological targeting of the Notch pathway could inhibit pancreatic tumor growth and potentiate gemcitabine sensitivity. In vitro, MRK-003 treatment downregulated the canonical Notch target gene Hes-1, significantly inhibited anchorage independent growth, and reduced the subset of CD44+CD24+ and aldehyde dehydrogenase (ALDH)+ cells that have been attributed with tumor initiating capacity. Ex vivo pretreatment of PDAC cells with MRK-003 in culture significantly inhibited the subsequent engraftment in immunocompromised mice. In vivo, MRK-003 monotherapy significantly blocked tumor growth in 5 of 9 (56%) patient-derived PDAC xenografts. Moreover, a combination of MRK-003 and gemcitabine showed enhanced antitumor effects compared to gemcitabine alone in 4 of 9 (44%) PDAC xenografts. Baseline gene expression analysis of the treated xenografts indicated that upregulation of nuclear factor kappa B (NFB) pathway components was associated with the sensitivity to single MRK-003, while upregulation in B-cell receptor (BCR) signaling and nuclear factor erythroid-derived 2-like 2 (NRF2) pathway correlated with response to the combination of MRK-003 with gemcitabine. The preclinical findings presented here provide further rationale for small molecule inhibition of Notch signaling as a therapeutic strategy in PDAC.
Publication Title
The gamma secretase inhibitor MRK-003 attenuates pancreatic cancer growth in preclinical models.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Trophoblast stem cells (TS cells), derived from the trophectoderm (TE) of blastocysts, require transcription factors (TFs) and external signals (Fgf4, Activin/Nodal/Tgfb) for self-renewal. While many reports have focused on TF networks that regulate embryonic stem cell (ES cell) self-renewal and pluripotency, little is know about TF networks that regulate self-renewal in TS cells. To further understand transcriptional networks in TS cells we used chromatin immunopreciptiation and DNA microarray analysis (ChIP-chip) to investigate targets of TFs Ap-2g (Tcfap2c), Eomes, Ets2, and Gata3, and a chromatin remodeling factor, Brg1 (Smarca4). We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide analysis of histone H3 acetylation (AcH3). Our results describe previously unknown transcriptional networks in TS cells, including TF occupancy of genes involved in ES cell self-renewal and pluripotency, co-occupancy of multiple TFs at target genes, and transcriptional regulatory circuitry within the 5 factors. Through genome-wide mapping and global expression analysis of 5 TF target genes, our data provide a comprehensive analysis of transcriptional networks that regulate TS cell self-renewal.
Publication Title
Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Epigenetic regulation of gene expression is important in maintaining self-renewal of embryonic stem (ES) cells and trophoblast stem (TS) cells. Histone deacetylases (HDACs) negatively control histone acetylation by removing covalent acetylation marks from histone tails. Because histone acetylation is a known mark for active transcription, HDACs presumably associate with inactive genes. Here, we used genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES cells and TS cells. Through evaluation of genes associated with acetylated histone H3 marks, and global expression analysis of Hdac1 knockout ES cells and trichostatin A treated ES cells and TS cells, we found that HDAC1 occupies mainly active genes, including important regulators of ES cell and TS cell self-renewal. By mapping HDAC1 targets on a global scale, our results describe further insight into epigenetic mechanisms of ES cell and TS cell self-renewal.
Publication Title
HDAC1 regulates pluripotency and lineage specific transcriptional networks in embryonic and trophoblast stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Saccharomyces cerevisiae
- 31 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
determination of gene regulation by sterol and sphingolipid composition
Publication Title
Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology.
Sample Metadata Fields
Sex
View Samples- Saccharomyces cerevisiae
- 25 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
These Affymetrix data were used to determine the role of each non-essential subunit of the conserved Ccr4-Not complex in the control of gene expression in the yeast S. cerevisiae. The study was performed with cells growing exponentially in high glucose and with cells grown to glucose depletion. Specific patterns of gene de-regulation were observed upon deletion of any given subunit, revealing the specificity of each subunits function. Consistently, the purification of the Ccr4-Not complex through Caf40p by tandem affinity purification from wild-type cells or cells lacking individual subunits of the Ccr4-Not complex revealed that each subunit had a particular impact on complex integrity. Furthermore, the micro-arrays revealed that the role of each subunit was specific to the growth conditions. From the study of only two different growth conditions, revealing an impact of the Ccr4-Not complex on more than 85% of all studied genes, we can infer that the Ccr4-Not complex is important for expression of most of the yeast genome.
Publication Title
Specific roles for the Ccr4-Not complex subunits in expression of the genome.
Sample Metadata Fields
No sample metadata fields
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