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.
Specific roles for the Ccr4-Not complex subunits in expression of the genome.
No sample metadata fields
View SamplesGene expression profiling has been performed previously on motor cortex and spinal cord homogenates and of sporadic ALS cases and controls, to identify genes and pathways differentially expressed in ALS. More recent studies have combined the use of laser capture microdissection (LCM) with gene expression profiling to isolate the motor neurons from the surrounding cells, such as microglia and astrocytes, in order to determine those genes differentially expressed in the vulnerable cell population i.e. motor neuron.
Phosphatase and tensin homologue/protein kinase B pathway linked to motor neuron survival in human superoxide dismutase 1-related amyotrophic lateral sclerosis.
Specimen part, Disease
View SamplesHigh-protein diets are known to reduce adiposity in the context of high carbohydrate and Western diets. However, few studies have investigated the specific high-protein effect on lipogenesis induced by a high-sucrose (HS) diet or fat deposition induced by high-fat feeding. We aimed to determine the effects of high protein intake on the development of fat deposition and partitioning in response to high-fat and/or HS feeding. A total of thirty adult male Wistar rats were assigned to one of the six dietary regimens with low and high protein, sucrose and fat contents for 5 weeks. Body weight (BW) and food intake were measured weekly. Oral glucose tolerance tests and meal tolerance tests were performed after 4th and 5th weeks of the regimen, respectively. At the end of the study, the rats were killed 2 h after ingestion of a calibrated meal. Blood, tissues and organs were collected for analysis of circulating metabolites and hormones, body composition and mRNA expression in the liver and adipose tissues. No changes were observed in cumulative energy intake and BW gain after 5 weeks of dietary treatment. However, high-protein diets reduced by 20 % the adiposity gain induced by HS and high-sucrose high-fat (HS-HF) diets. Gene expression and transcriptomic analysis suggested that high protein intake reduced liver capacity for lipogenesis by reducing mRNA expressions of fatty acid synthase (fasn), acetyl-CoA carboxylase a and b (Acaca and Acacb) and sterol regulatory element binding transcription factor 1c (Srebf-1c). Moreover, ketogenesis, as indicated by plasma -hydroxybutyrate levels, was higher in HS-HF-fed mice that were also fed high protein levels. Taken together, these results suggest that high-protein diets may reduce adiposity by inhibiting lipogenesis and stimulating ketogenesis in the liver.
High dietary protein decreases fat deposition induced by high-fat and high-sucrose diet in rats.
Sex, Specimen part
View SamplesEffect of high fat diet feeding on gene expression
Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice.
Sex, Age, Specimen part, Subject
View SamplesDevelopmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors. Although cellular metabolism plays an important role, little is known how it changes during human neurogenesis, and how potential alterations affect toxicant sensitivity of mature vs. immature neurons. We used immature (d0) and mature (d6) LUHMES cells (dopaminergic human neurons) to provide initial answers to these questions. Transcriptome profiling and characterization of energy metabolism suggested a switch from predominantly glycolytic energy generation to a more pronounced contribution of the tricarboxylic acid cycle (TCA) during neuronal maturation. Therefore, we used pulsed stable isotope-resolved metabolomics (pSIRM) to determine intracellular metabolite pool sizes (concentrations), and isotopically non-stationary 13C-metabolic flux analysis (INST 13C MFA) to calculate metabolic fluxes. We found that d0 cells mainly use glutamine to fuel the TCA. Furthermore, they rely on extracellular pyruvate to allow continuous growth. This metabolic situation does not allow for mitochondrial or glycolytic spare capacity, i.e. the ability to adapt energy generation to altered needs. Accordingly, neuronal precursor cells displayed a higher sensitivity to several mitochondrial toxicants than mature neurons differentiated from them. In summary, this study shows that precursor cells lose their glutamine dependency during differentiation while they gain flexibility of energy generation and thereby increase their resistance to low concentrations of mitochondrial toxicants.
Stage-specific metabolic features of differentiating neurons: Implications for toxicant sensitivity.
Sex, Specimen part, Time
View SamplesMouse ES cells were differentiated for 6 days. Undifferentiated cells (d0) were compared to cells harvested at 24 hour timepoints (d1-d6).
Transcriptional profiling of mouse and human ES cells identifies SLAIN1, a novel stem cell gene.
Age, Specimen part, Cell line, Time
View SamplesUndifferentiated cells of different passage numbers (p19 and p128) were compared to cells differentiated in hanging drops for 5 days (d5 embryoid bodies) or expanded on gelatin coated dishes for a further 9 days (d14 embryoid bodies).
Transcriptional profiling of mouse and human ES cells identifies SLAIN1, a novel stem cell gene.
Age, Specimen part, Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Role of TAZ as mediator of Wnt signaling.
Cell line, Treatment
View SamplesTo investigate the role of TAZ downstream of APC and beta-catenin in mammary epithelial cells cells, we compared the expression profiles of MCF10-T1k (MII) cells transfected with siControl, siAPC, siAPC+siTAZ, sibeta-catenin, or sibeta-catenin+siTAZ.
Role of TAZ as mediator of Wnt signaling.
Cell line, Treatment
View SamplesTo investigate the role of TAZ downstream of the abberrant Wnt signaling in CRC cells, we compared the expression profiles of parental SW480 cells (empty vector) transfected with siControl, siTAZ, sibeta-catenin or reconstituted with wild type APC and transfected with siControl
Role of TAZ as mediator of Wnt signaling.
Cell line, Treatment
View Samples