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GSE7500
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cell-and context-specific activities of nuclear receptors may in part be due to distinct coregulator complexes recruited to distinct subsets of target genes. RIP140 (also called NRIP1) is a ligand-dependent corepressor that is inducible with retinoic acid (RA). We have shown previously that silencing of RIP140 enhances RA-induced differentiation and enhances the induction of model RA target genes in human embryonal carcinoma cells (EC). Through use of microarray technology we sought to elucidate in a de novo fashion the global role of RIP140 in RA-dependent signaling. RIP140-dependent gene expression was largely consistent with RIP140 functioning to limit RAR signaling. Few if any genes were regulated in a manner to support a role for RIP140 in active repression. Interestingly, approximately half of the RA-dependent genes were unaffected by RIP140, suggesting that RIP140 may discriminate between different classes of RA target genes. RIP140 silencing also accelerated RA target gene activation and sensitized EC cells to low doses of RA. Together the data suggests that the RIP140-dependent RA target genes identified here may be particularly important in mediating RA-induced tumor cell differentiation. RIP140 may be an attractive target to sensitize tumor cells to retinoid-based differentiation therapy.
Publication Title
Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
FVB mice were engineered to express wild-type human cyclin E under control of the human surfactant C promoter (CEO mice; Ma et al, PNAS 2007). These mice develop spontaneous lung tumors, which were shown to be adenocarcinoma by histological analysis. Here we compare whole-genome RNA expression levels between the tumors and normal lung of 4 CEO mice as well as 4 nontransgenic animals.
Publication Title
Evidence for tankyrases as antineoplastic targets in lung cancer.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The specialisation of mammalian cells in time and space requires genes associated with specific pathways and functions to be co-ordinately expressed. Here we have combined a large number of publically available microarray datasets (745 samples, from over 100 separate studies) derived from human primary cells and analysed on the Affymetrix U133plus2.0 array. Using the network analysis tool BioLayout Express3D we have constructed and clustered large correlation graphs of these data in order to identify robust co-associations of genes expressed in a wide variety of cell lineages. We discuss the biological significance of a number of these associations, in particular the coexpression of key transcription factors with the genes that they are likely to control. We consider the regulation of genes in human primary cells and specifically in the human mononuclear phagocyte system. Of particular note is the fact that these data do not support the identity of putative markers of antigen-presenting dendritic cells, nor classification of M1 and M2 activation states, a current subject of debate within immunological field. We have provided this data resource on the BioGPS web site (www.biogps.org) and on macrophages.com (www.macrophages.com).
Publication Title
An expression atlas of human primary cells: inference of gene function from coexpression networks.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 64 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
The activation profiles of macrophages under different immune and inflammatory conditions have generated great interest. LPS, in particular, is a commonly used in vitro model of infection and inflammation studies in macrophages. We have used gene expression microarrays to define the effects of each of three variables; LPS dose, LPS vs. interferons beta and gamma, and genetic background on the transcriptional response of mouse bone marrow-derived macrophages
Publication Title
Analysis of the transcriptional networks underpinning the activation of murine macrophages by inflammatory mediators.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 86 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st), Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Assembly of a Parts List of the Human Mitotic Cell Cycle Machinery.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Conjunctival samples from 60 individuals with and without the clinical signs of active trachoma were analysed on the U133 Plus 2.0 arrays. Global transcriptional changes characteristic of disease and infection phenotypes were identified. Two analysis methods found large numbers of differentially regulated genes and the existence of networks of co-expressed genes. There were signatures characteristic of the host defence response with evidence supporting infiltration of various types of leukocytes and activation of innate responses of epithelial cells. Two separate methods could classify disease and infection phenotype based on transcription signatures with 70% accuracy. These results provide an insight into the complexity of the acute response in trachoma but are able to partly explain the biology of trachoma through the identification of pathways and gene expression sets useful to future studies on chlamydial immunopathogenesis.
Publication Title
Human conjunctival transcriptome analysis reveals the prominence of innate defense in Chlamydia trachomatis infection.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Race
View Samples- Homo sapiens
- 36 Downloadable Samples
Illumina HiSeq 2000
Description
Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes, promote tumor cell growth, increase cancer 'stemness' and chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression. Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Carcinoma-associated mesenchymal stem cells (CA-MSCs) are critical stromal progenitor cells within the tumor microenvironment. We previously demonstrated that CA-MSCs differentially express BMP genes, promote tumor cell growth, increase cancer 'stemness' and chemotherapy resistance. Here we use RNA sequencing of normal omental MSCs and ovarian CA-MSCs to demonstrate CA-MSCs have global changes in gene expression. Using these expression profiles we create a unique predictive algorithm to classify CA-MSCs. Our classifier, accurately distinguishes normal omental, ovary and bone marrow MSCs from ovarian cancer CA-MSCs. Suggesting broad applicability, the model correctly classifies pancreatic and endometrial cancer CA-MSCs and distinguishes cancer associated fibroblasts (CAFs) from CA-MSCs. Using this classifier, we definitively demonstrate ovarian CA-MSCs arise from tumor mediated reprograming of local tissue MSCs. While cancer cells alone cannot induce a CA-MSC phenotype, the in vivo ovarian tumor micoenvironment (TME) can reprogram omental or ovary MSCs to protumorigenic CA-MSC (classifier score of >0.96). In vitro studies suggest that both tumor secreted factors and hypoxia are critical to induce the CA-MSC phenotype. Interestingly, while the breast cancer TME can reprogram BM MSCs into CA-MSCs, the ovarian TME cannot, demonstrating for the first time that tumor mediated CA-MSC conversion is tissue and cancer type dependent. Together these findings (1) provide a critical tool to define CA-MSCs and (2) highlight cancer cell influence on distinct normal tissues providing powerful insights into the mechanisms underlying cancer specific metastatic niche formation. Overall design: mRNA profiles of 4 normal omental MSCs and 10 ovarian CA-MSCs using Illumina TruSeq RNA Sample Preparation kit and Illumina HiSeq 100bp PE sequencing.
Publication Title
Ovarian Carcinoma-Associated Mesenchymal Stem Cells Arise from Tissue-Specific Normal Stroma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Transcriptional programmes involved in the eukaryotic cell cycle are activated sequentially throughout the process. In particular, the set of genes required for S and G2-M phases are highly conserved and induced one after the other.
Publication Title
Assembly of a Parts List of the Human Mitotic Cell Cycle Machinery.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
In order to study the microglia contribution in neurodegeneration more specifically we established a mouse model of prion disease in which the 79A murine prion strain was introduced by an intraperitoneal route into BALB/cJFms-EGFP/- mice, which express Enhanced Green Fluorescent Protein (EGFP) under control of the C-fms operon. Samples were taken at time points during disease progression and histological analysis of the brain and transcriptional analysis of isolated microglia was carried out. The analysis of isolated microglia revealed a disease specific, highly pro-inflammatory signature in addition to an up-regulation of genes associated with metabolism, respiratory stress and DNA repair. This study strongly supports the growing recognition of the importance of microglia within the prion disease process and identifies the nature of the response through gene expression analysis of isolated microglia.
Publication Title
Defining the Microglia Response during the Time Course of Chronic Neurodegeneration.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 14 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Non-steroidal anti-inflammatory drugs (NSAIDs) are used extensively as therapeutic agents, despite their well-documented gastrointestinal (GI) toxicity. Presently, the mechanisms responsible for NSAID-associated GI damage are incompletely understood. In this study, we used Microarray analysis to generate a novel hypothesis about cellular mechanisms that underlie the GI toxicity of NSAIDs. Monolayers of intestinal epithelial
Publication Title
Drug-induced alterations to gene and protein expression in intestinal epithelial cell 6 cells suggest a role for calpains in the gastrointestinal toxicity of nonsteroidal anti-inflammatory agents.
Sample Metadata Fields
Specimen part
View Samples