Hepatitis C Virus is a leading cause of chronic liver disease. The identification and characterisation of key host cellular factors that play a role in the HCV replication cycle is important for the understanding of disease pathogenesis and the identification of novel anti-viral therapeutic targets. Gene expression profiling of HCV infected Huh7 cells by microarray analysis was performed to identify host cellular genes that are transcriptionally regulated by infection. The expression of host genes involved in cellular defence mechanisms (apoptosis, proliferation and anti-oxidant responses), cellular metabolism (lipid and protein metabolism) and intracellular transport (vesicle trafficking and cytoskeleton regulation) was significantly altered by HCV infection. The gene expression patterns identified provide insight into the potential mechanisms that contribute to HCV associated pathogenesis. These include an increase in pro-inflammatory and pro-apoptotic signalling and a decrease in the anti-oxidant response pathways of the infected cell.
Gene expression profiling indicates the roles of host oxidative stress, apoptosis, lipid metabolism, and intracellular transport genes in the replication of hepatitis C virus.
Specimen part, Cell line
View SamplesGrowing evidence indicates that PPAR agonists, such as rosiglitazone (RSG,), induce adipose mitochondrial biogenesis. Using microarrays, we systematically analyzed nucleus-encoded mitochondrial gene expression in two common murine adipocyte models, 3T3 L1 and C3H/10T1/2 adipocytes, and aimed to further establish the direct role of RSG, and capture the temporal changes in mitochondrial gene transcription during this process.
Rosiglitazone Induces Mitochondrial Biogenesis in Differentiated Murine 3T3-L1 and C3H/10T1/2 Adipocytes.
Specimen part
View SamplesMolecular pathways activated in MALT lymphoma are not well defined.
Gene expression profiling of pulmonary mucosa-associated lymphoid tissue lymphoma identifies new biologic insights with potential diagnostic and therapeutic applications.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.
Specimen part, Time
View SamplesCircadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erb , a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes. Here we show that Rev-erb modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erb to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erb regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erb and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erb utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue.
GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sex, Age, Cell line, Treatment
View SamplesWe have used primary MEFs derived from wild type and E2F4 null mice growing asynchrounously in serum to generate a signature for E2F4 pathway activation. 10 wild type and 10 E2F4 null samples were each assayed using the Affymetrics Mouse Genome 430A 2.0 array.
Patterns of cell signaling pathway activation that characterize mammary development.
No sample metadata fields
View SamplesThe aim of this study was to identify differential gene expression in lung T cell subsets upon germline Serpinb1a ablation.
SerpinB1 regulates homeostatic expansion of IL-17+ γδ and CD4+ Th17 cells.
Specimen part
View SamplesCohesin, which consists of SMC1, SMC3, Rad21 and either SA1 or SA2, topologically embraces the chromatin fibers to hold sister chromatids together and to stabilize chromatin loops. Increasing evidence indicates that these loops are the organizing principle of higher-order chromatin architecture, which in turn is critical for gene expression. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expression and chromatin architecture in cerebral cortex and pancreas from adult mice. More than one third of cohesin binding sites differ between the two tissues and these are enriched at the regulatory regions of tissue-specific genes. Cohesin colocalizes extensively with the CCCTC-binding factor (CTCF). Cohesin/CTCF sites at active enhancers and promoters contain, at least, cohesin-SA1 whereas either cohesin-SA1 or cohesin-SA2 are present at active promoters independently of CTCF. Analyses of chromatin contacts at the Protocadherin gene cluster and the Regenerating islet-derived (Reg) gene cluster, mostly expressed in brain and pancreas respectively, revealed remarkable differences in the architecture of these loci in the two tissues that correlate with the presence of cohesin. Moreover, we found decreased binding of cohesin and reduced transcription of the Reg genes in the pancreas of SA1 heterozygous mice. Given that Reg proteins are involved in the control of inflammation in pancreas, such reduction may contribute to the increased incidence of pancreatic cancer reported in these animals. Overall design: Examination of the relationship between gene expression, genome wide cohesin distribution and chromatin structure
The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues.
No sample metadata fields
View SamplesCirculating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that human high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Highly-purified fractions of human HDL contain small RNAs, and the HDL-miRNA profile from normal subjects is significantly different than familial hypercholesterolemia subjects. miRNAs were demonstrated to associate with both native and reconstituted HDL particles, and reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. Furthermore, HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of mRNA reporters. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations suggest that HDL participates in a novel mechanism of intercellular communication involving the transport and delivery of miRNAs.
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Cell line, Treatment
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