We examined the effect of ablation of Tet2, an epigenetic regulator of gene transcription, in the global programme of gene expression at baseline, without pro-inflammatory activation, in macrophages.
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.
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View SamplesWe examined the effect of ablation of Tet2, an epigenetic regulator of gene transcription, in the global programme of gene expression underlying pro-inflammatory activation of macrophage.
Clonal hematopoiesis associated with TET2 deficiency accelerates atherosclerosis development in mice.
Specimen part
View SamplesAlthough gain of chromosome-5p is one of the most frequent DNA copy number imbalances in cervical squamous cell carcinoma (SCC), the genes that drive its selection remain poorly understood. In a previous cross-sectional clinical study we showed that the microRNA processor Drosha (located on chromosome-5p) demonstrates frequent copy-number gain and over-expression in cervical SCC, associated with altered microRNA profiles. Here, we have conducted gene depletion/over-expression experiments to demonstrate the functional significance of up-regulated Drosha in cervical SCC cells. Drosha depletion by RNA-interference (RNAi) produced significant, specific reductions in cell motility/invasiveness in vitro, with a silent RNAi-resistant Drosha mutation providing phenotype rescue. Unsupervised hierarchical clustering following global profiling of 319 microRNAs in eighteen cervical SCC cell line specimens generated two groups according to Drosha expression levels. Altering Drosha levels in individual SCC lines changed the group into which the cells clustered, with gene depletion effects being rescued by the RNAi-resistant mutation. Forty-five microRNAs showed significant differential expression between the groups, including four of fourteen that were differentially-expressed in association with Drosha levels in clinical samples. miR-31 up-regulation in Drosha over-expressing samples/cell lines was the highest-ranked change (by adjusted p-value) in both analyses, an observation validated by Northern blotting. These functional data support the role of Drosha as an oncogene in cervical SCC, by affecting expression of cancer-associated microRNAs that have the potential to regulate numerous protein-coding genes.
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sex, Cell line
View SamplesComparison of mRNA expression profiles in W12 Series 1 cervical ectokeratinocytes at passage number 22 versus 19 (during which time the cells gain an invasive phenotype)
Functional evidence that Drosha overexpression in cervical squamous cell carcinoma affects cell phenotype and microRNA profiles.
Sex, Cell line
View SamplesThe liver is one of most important organs in our bodies. It performs many essential functions including metabolism, synthesis, secretion, detoxification, and storage. Hepatocytes are the principal cell type in the liver and are involved in multiple liver-specific functions. There have been several efforts to develop in vitro culture systems capable of maintaining hepatocyte-specific phenotype over long time periods. In hepatic tissue engineering, two commonly used culture systems are the collagen sandwich and monolayers of cells. In this study, genome-wide gene expression profiles of primary hepatocytes were measured over an 8-day period for each cell culture system using Affymetrix GeneChips and analyzed via Gene Set Enrichment Analysis (GSEA), which is a powerful method to elicit biologically meaningful information from microarray data at the level of gene sets. Results indicate that the gene expression in hepatocytes in collagen sandwich cultures gradually diverges from that in monolayer cultures. Gene sets up-regulated in collagen sandwich cultures include those associated with liver metabolic and synthetic functions. These functions are associated with lipid, amino acid, carbohydrate, and alcohol metabolism and bile acid synthesis. Nuclear receptors are up-regulated in collagen sandwiches 24 hours after seeding. Signals transmitted from these receptors may cause the up-regulation of other processes in subsequent days. Cytochrome-P450 monooxygenase expression was initially down-regulated but exhibited up-regulation after 72 hours. Our results provide a baseline for further explorations into the systems biology of engineered liver mimics as well as 2D and 3D co-cultures of primary hepatocytes and non-parenchymal cells.
A comparative study of genome-wide transcriptional profiles of primary hepatocytes in collagen sandwich and monolayer cultures.
Specimen part
View SamplesIn this study, genome-wide gene expression profiles of primary hepatocytes and liver sinusoidal endothelial cells (LSECs) were measured at day 12 for each cell culture system using Affymetrix GeneChips and analyzed via Gene Set Enrichment Analysis (GSEA). The culture systems analyzed include the commonly used collagen sandwich and monolayers of hepatocytes, as well as 3-dimensional (3D) engineered liver models that contain hepatocytes and LSECs (3DHL) and hepatocytes, LSECs, and Kupffer cells (3DHLK). Our results highlight the up-regulation of several hepatocyte specific functions in hepatocytes and a novel interplay between Ppara signaling and bile acid biosynthesis in LSECs.
Transcriptomic Analysis of Hepatic Cells in Multicellular Organotypic Liver Models.
Specimen part, Time
View SamplesThe type II Oncostatin M receptor (OSMR) serves as the main binding site for the pleiotropic cytokine OSM. We have previously demonstrated a positive correlation between copy number driven OSMR over-expression and adverse clinical outcome in cervical tumours and have also established enhanced angiogenic, migratory and invasive potential as major consequences of OSMR over-expression using cell-line models of cervical cancer. By analysis of gene expression patterns in cell lines and tumours, this study now systematically defines cohorts of genes that are implicated for the phenotypes observed. Importantly, we have identified 15 OSM induced genes that are involved in at least one of these key functions and are up-regulated in both OSMR over-expressing cell-lines and tumours. These genes can serve as markers of OSM signalling in OSMR over-expressing SCCs and represent suitable targets for functional characterisation.
Overexpression of the oncostatin M receptor in cervical squamous cell carcinoma cells is associated with a pro-angiogenic phenotype and increased cell motility and invasiveness.
Sex, Cell line, Time
View SamplesWe sought to apply the technologies of gene expression profiling to detect genes significant in the aetiology of cervical carcinoma . We investigated 14 normal (NAD), 11 low grade squamous intrapepithelial lesions (LSIL), 21 high grade squamous intraepithelial lesions (HSIL) and 28 squamous cell carcinomas by Affymetrix GeneChip whole transcriptome profiling. Two SCC cell lines were also included in the cohort. Normal and SILS were profiled using the Affymetrix U133A platform, while SCCs and Cell lines were profiled using the Affymetrix U133A plus 2.0 array.
Gain and overexpression of the oncostatin M receptor occur frequently in cervical squamous cell carcinoma and are associated with adverse clinical outcome.
Specimen part, Cell line
View SamplesWe used microarray analysis to examine which genes are differentially expressed in mice that received a combination of fish oil and indomethacin.
Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR(-/-) mice.
Specimen part, Compound
View SamplesComparison of miRNA expression profiles in malignant germ cell tumors compared to non-malignant control group.
Malignant germ cell tumors display common microRNA profiles resulting in global changes in expression of messenger RNA targets.
Sex, Age
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