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GSE70126
Mus musculus
8 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
Formation of foam cell macrophages (FCMs), which sequester extracellular modified lipids, is a key event in atherosclerosis. How lipid loading affects macrophage phenotype is controversial, with evidence suggesting either pro- or anti-inflammatory consequences. To investigate this further, we compared the transcriptomes of foamy and non-foamy macrophages (NFMs) that accumulate in the subcutaneous granulomas of fed-fat ApoE null mice and normal chow fed wild-type mice in vivo. Consistent with previous studies, LXR/RXR pathway genes were significantly over-represented among the genes up-regulated in foam cell macrophages. Unexpectedly, the hepatic fibrosis pathway, associated with platelet derived growth factor and transforming growth factor- action, was also over-represented. Several collagen polypeptides and proteoglycan core proteins as well as connective tissue growth factor and fibrosis-related FOS and JUN transcription factors were up-regulated in foam cell macrophages. Increased expression of several of these genes was confirmed at the protein level in foam cell macrophages from subcutaneous granulomas and in atherosclerotic plaques. Moreover, phosphorylation and nuclear translocation of SMAD2, which is downstream of several transforming growth factor- family members, was also detected in foam cell macrophages. We conclude that foam cell formation in vivo leads to a pro-fibrotic macrophage phenotype, which could contribute to plaque stability, especially in early lesions that have few vascular smooth muscle cells.
Publication Title
Foam Cell Formation In Vivo Converts Macrophages to a Pro-Fibrotic Phenotype.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Testosterone production by Leydig cells is a tightly regulated process requiring synchronized expression of several steroidogenic genes by numerous transcription factors. Myocyte enhancer factor 2 (MEF2) is a transcription factor recently identified in somatic cells of the male gonad. In other tissues, MEF2 is an essential regulator of organogenesis and cell differentiation. So far in the testis, MEF2 was found to regulate Leydig cell steroidogenesis by controlling Nr4a1 and Star gene expression. To expand our understanding of the role of MEF2 in Leydig cells, we performed microarray analyses of MA-10 Leydig cells depleted in MEF2 and results were analyzed using the Partek and IPA softwares. Several genes were differentially expressed in MEF2-depleted Leydig cells and 15 were validated by qPCR. A large number of these genes are known to be involved in fertility, gonad morphology and steroidogenesis and include Pde8a, Por, Ahr, Bmal1, Cyp1a1, Cyp1b1, Map2k1, Tsc22d3, Nr0b2, Smad4, and Star, which were all downregulated in the absence of MEF2. In silico analyses revealed the presence of MEF2 binding sites within the first 2 kb upstream the transcription start site of the Por, Bmal1, and Nr0b2 promoters, which suggests a direct regulation by MEF2. Using transient transfections in MA-10 Leydig cells, siRNA knockdown, and a MEF2-Engrailed dominant negative, we found that MEF2 activates the Por, Bmal1 and Nr0b2 promoters and that this requires an intact MEF2 element. Our results identify novel target genes for MEF2 and define MEF2 as an important regulator of Leydig cell function and male reproduction.
Publication Title
Novel Targets for the Transcription Factors MEF2 in MA-10 Leydig Cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Proper mitochondrial function plays a central role in cellular metabolism. Various diseases as well as aging are associated with diminished mitochondrial function. Previously, we identified 19 miRNAs putatively involved in the regulation of mitochondrial metabolism in skeletal muscle, a highly metabolically active tissue. In the present study, these 19 miRNAs were individually silenced in C2C12 myotubes using antisense oligonucleotides, followed by measurement of the expression of 27 genes known to play a major role in regulating mitochondrial metabolism. Based on the outcomes, we then focused on miR-382-5p and identified pathways affected by its silencing using microarrays, investigated protein expression and studied cellular respiration. Silencing of miRNA-382-5p significantly increased the expression of several genes involved in mitochondrial dynamics and -biogenesis. Microarray analysis of C2C12 myotubes silenced for miRNA-382-5p revealed a collective downregulation of mitochondrial ribosomal proteins and respiratory chain proteins. This effect was accompanied by an imbalance between mitochondrial proteins encoded by the nuclear and mitochondrial DNA (1.35-fold, p<0.01) and an induction of HSP60 protein (1.31-fold, p<0.05), indicating activation of the mitochondrial unfolded protein response (mtUPR). Furthermore, silencing of miR-382-5p reduced basal oxygen consumption rate by 14% (p<0.05) without affecting mitochondrial content, pointing towards a more efficient mitochondrial function as a result of improved mitochondrial quality control. Taken together, silencing of miR-382-5p induces a mitonuclear protein imbalance and activates the mtUPR in skeletal muscle, a phenomenon that was previously associated with improved longevity.
Publication Title
MicroRNA-382 silencing induces a mitonuclear protein imbalance and activates the mitochondrial unfolded protein response in muscle cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epithelial-mesenchymal transition has been implicated in tumor metasisi, cancer drug resistance and cancer stem cell features. In this study, we examined gene expression profiles of three non-small cell lung cancer cell lines, before and after experimentally induced EMT.
Publication Title
Metabolic and transcriptional profiling reveals pyruvate dehydrogenase kinase 4 as a mediator of epithelial-mesenchymal transition and drug resistance in tumor cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
A small number of tumor-derived cell lines have formed the mainstay of cancer therapeutic development, yielding drugs with impact typically measured as months to disease progression. To develop more effective breast cancer therapeutics, and more readily understand their potential clinical impact, we constructed a functional metabolic portrait of 46 independently-derived breast tumorigenic cell lines, contrasted with purified normal breast epithelial subsets, freshly isolated pleural effusion breast tumor samples and culture-adapted, non-tumorigenic mammary epithelial cell derivatives. We report our analysis of glutamine uptake, dependence, and identification of a significant subset of triple negative samples that are glutamine auxotrophs. This NCBI GEO submission comprises a small datasest generated to compare the expression profiles of the above nontumorigenic, purified normal and purified pleural effusion samples with 10 established breast cancer-derived cell lines. This dataset was subsequently merged with a previously published expression dataset derived from 45 independent breast cancer derived cell lines (Neve, et al 2006), and analyses contrasting various subsets of the merged dataset were published.
Publication Title
Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 116 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lymph node involvement is the most important prognostic factor in breast cancer, but little is known about the underlying molecular changes. First, to identify a molecular signature associated with nodal metastasis, gene expression analysis was performed on a homogeneous group of 96 primary breast tumors, balanced for lymph node involvement. Each tumor was diagnosed as a poorly differentiated, estrogen positive, her2-neu negative invasive ductal cancer. (Affymetrix Human U133 Plus 2.0 microarray chips). A model, including 241 genes was built and validated on an internal and external dataset performed with Affymetrix technology. All samples used for validation had the same characteristics as the initial tumors. The area under the ROC curve (AUC) for the internal dataset was 0.646 and 0.651 for the external datasets. Thus, the molecular profile of a breast tumor reveals information about lymph node involvement, even in a homogeneous group of tumors. However, an AUC of 0.65 indicates only a weak correlation. Our model includes multiple kinases, apoptosis related and zinc ion binding genes. Pathway analysis using the Molecular Signatures Database revealed relevant gene sets (BAF57, Van 't Veer). Next, miRNA profiling was performed on 82/96 tumors using Human MiRNA microarray chips (Illumina). Eight miRNAs were significantly differentially expressed according to lymph node status at a significance level of 0.05, without correcting for multiple testing. The analysis of the inverse correlation between a miRNA and its computationally predicted targets point to general deregulation of the miRNA machinery potentially responsible for lymph node invasion. In conclusion, our results provide evidence that lymph node involvement in breast cancer is not a random process.
Publication Title
Prediction of lymph node involvement in breast cancer from primary tumor tissue using gene expression profiling and miRNAs.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 284 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Histological classification of gliomas guides treatment decisions. Because of the high interobserver variability, we aimed to improve classification by performing gene expression profiling on a large cohort of glioma samples of all histological subtypes and grades. The seven identified intrinsic molecular subtypes are different from histological subgroups and correlate better to patient survival. Our data indicate that distinct molecular subgroups clearly benefit from treatment. Specific genetic changes (EGFR amplification, IDH1 mutation, 1p/19q LOH) segregate in -and may drive- the distinct molecular subgroups. Our findings were validated on three large independent sample cohorts (TCGA, REMBRANDT, and GSE12907). We provide compelling evidence that expression profiling is a more accurate and objective method to classify gliomas than histology.
Publication Title
Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 64 Downloadable Samples
IlluminaGenomeAnalyzerIIx
Description
56 breast cancer cell lines were profiled to identify patterns of gene expression associated with subtype and response to therapeutic compounds. Overall design: Cell lines were profiled in their baseline, unperturbed state.
Publication Title
Modeling precision treatment of breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
We are investigating the transcriptional response of Anc1 deficient yeast under basal and MMS exposed conditions
Publication Title
Anc1, a protein associated with multiple transcription complexes, is involved in postreplication repair pathway in S. cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The final size of plant organs such as leaves is tightly controlled by environmental and genetic factors that must spatially and temporally coordinate cell expansion and cell cycle activity. However this regulation of organ growth is still poorly understood. The aim of this study is to gain more insight in the genetic control of leaf size in Arabidopsis by performing a comparative analysis of transgenic lines that produce larger leaves under standardized environmental conditions. To this end, we selected five genes, belonging to different functional classes, that all positively affect leaf size when over-expressed: AVP1, GRF5, JAW, BRI1 and GA20OX1. We show that the increase in leaf area in these lines depends on leaf position and growth conditions and that all five lines affect leaf size differently. However, in all cases an increase in cell number is, entirely or predominantly, responsible for the leaf size enlargement. By means of analyses of hormone levels, transcriptome and metabolome we provide deeper insight in the molecular basis of the growth phenotype for the individual lines. A comparative analysis between them indicates that enhanced organ growth is governed by different, seemingly independent pathways. The analysis of transgenic lines simultaneously over-expressing two growth-enhancing genes further supports the concept that multiple pathways independently converge on organ size control in Arabidopsis.
Publication Title
Increased leaf size: different means to an end.
Sample Metadata Fields
Specimen part
View Samples