This SuperSeries is composed of the SubSeries listed below.
GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis.
Specimen part, Cell line
View SamplesBoth bone morphogenetic proteins (BMPs) and histone deacetylases (HDACs) have previously been established to play a role in the development of the three major cell types of the central nervous system: neurons, astrocytes, and oligodendrocytes. We have previously established a connection between these two protein families, showing that HDACs suppress BMP-promoted astrogliogenesis in the embryonic striatum. Since HDACs act in the nucleus to effect changes in transcription, an unbiased analysis of their transcriptional targets could shed light on their downstream effects on BMP-signaling. Using neurospheres from the embryonic striatum as an in vitro system to analyze this phenomenon, we have performed microarray expression profiling on BMP2- and trichostatin A (TSA)-treated cultures, followed by validation of the findings with quantitative RT-PCR and protein analysis.
Distinct and overlapping gene regulatory networks in BMP- and HDAC-controlled cell fate determination in the embryonic forebrain.
Specimen part, Treatment
View SamplesRecent studies have reported that glycosphingolipids (GSL) might be involved in obesity induced insulin resistance. Those reports suggested that inhibition of GSL biosynthesis in animals ameliorated insulin sensitivity accompanied with improved glycemic control leading to decreased liver steatosis in obese mice. In addition, GSL depletion altered hepatic secretory function. In those studies, ubiquitously acting inhibitors for GSL-biosynthesis have been used to inhibit function of the enzyme Ugcg (UDP-glucose:ceramide glucosyltransferase), catalyzing the first step of the glucosylceramide based GSL-synthesis pathway. In the present study, a genetic approach for GSL deletion in hepatocytes was chosen to achieve full inhibition of GSL synthesis and to prevent possible adverse effects caused by Ugcg-inhibitors. Using the Cre/loxP system under control of the albumin promoter, GSL biosynthesis in hepatocytes and their release into the plasma could be effectively blocked. Deletion of GSL in hepatocytes did not change quantity of bile excretion through the biliary duct. Total bile salt content in bile-, feces- and plasma from mutant mice showed no difference as compared to control animals. Cholesterol concentration in liver-, bile-, feces- and plasma-samples remained unaffected. Lipoprotein concentration in plasma-samples in mutant animals reached similar levels as in their control littermates. No alteration in glucose tolerance after intraperitoneal application of glucose and insulin appeared in mutant animals. A preventive effect of GSL-deficiency on development of liver steatosis after high fat diet feeding could not be observed.
Hepatic glycosphingolipid deficiency and liver function in mice.
No sample metadata fields
View SamplesMyopathies and muscular dystrophies are devastating diseases sharing characteristic symp-toms. Little is known about common aetiopathology and biomarkers are rare. We studied skeletal muscle gene expression in mouse models of myopathies. As dystrophic processes in muscles are characterised by inflammatory processes, we expanded our analy-sis on a rat model of sepsis. We find 25 commonly dysregulated genes. Sarcolipin was upregulated most, exhibiting in-creased protein levels in different muscles as well as in rats treated with an inflammatory agent. Upregulation strongly correlated with disease status. Our findings suggest Sarcolipin as a potential biomarker and imply a new function in inflam-matory response.
No associated publication
Specimen part
View SamplesIn order to study the gene expression profile in C57Bl/10 mouse blood, we exposed three different groups of animals. First was exposed to PO2 21% or normoxia. The second was exposed to chronic hypoxia (from PO2 21% to PO2 8%) and the third was also exposed to the same chronic hypoxia (CH) protocol but followed by two weeks under normoxia, and called as recovery group. The blood was extracted from inferior vena cava, the RNA was extracted, amplified and hybridized to Affimetrix MOE 430 V2.o chip. The results were analyzed using Partek Genome suite software. Using two fold cuttoff and 0% FDR parameters, we observed genes 512 diferentially expressed, of which one gene was up-regulated in both hypoxic and recovery condition, 202 were up-regulated during CH and then down-regulated after the recovery, 18 genes were down-regulated afteh CH and the up-regulated after recovery, ans finally 9 genes were down-regulated in both CH and recovery conditions.
Expression profiling reveals novel hypoxic biomarkers in peripheral blood of adult mice exposed to chronic hypoxia.
Age
View SamplesThe -amyloid precursor protein APP and the related APLPs, undergo complex proteolytic processing giving rise to several fragments. Whereas it is well established that A accumulation is a central trigger for Alzheimer disease (AD), the physiological role of APP family members and their diverse proteolytic products is still largely unknown. The secreted APPs ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The -secretase generated APP intracellular domain AICD, functions as a transciptional regulator in heterologous reporter assays, although its role for endogenous gene regulation has remained controversial. To gain further insight into the molecular changes associated with knockout phenotypes and to elucidate the physiological functions of APP family members including their proposed role as transcriptional regulators we performed a DNA microarray transcriptome profiling of the frontal cortex of adult wild type, APP-/-, APLP2-/- and APPs knockin (KI) mice, APP/, expressing solely the secreted APPs ectodomain. Biological pathways affected by the lack of APP family members included regulation of neurogenesis, regulation of transcription and regulation of neuron projection development. Comparative analysis of transcriptome changes and qPCR validation identified co-regulated gene sets. Interestingly, these included heat shock proteins and plasticity related genes that were down-regulated in knock-out cortices. In contrast, we failed to detect significant differences in expression of previously proposed AICD target genes including Bace1, Kai1, Gsk3b, p53, Tip60 and Vglut2. Only Egfr was slightly up-regulated in APLP2-/- mice. Comparison of APP-/- and APP/ with wild-type mice revealed a high proportion of co-regulated genes indicating an important role of the C-terminus for cellular signaling. Finally, comparison of APLP2-/- on different genetic backgrounds revealed that background related transcriptome changes may dominate over changes due to the knockout of a single gene. Shared transcriptome profiles corroborated closely related physiological functions of APP family members in the adult central nervous system. As expression of proposed AICD target genes was not altered in adult cortex, this may indicate that these genes are not affected by lack of APP under resting conditions or only in a small subset of cells.
Comparative transcriptome profiling of amyloid precursor protein family members in the adult cortex.
Sex, Specimen part
View SamplesDespite its key role in Alzheimer pathogenesis, the physiological function(s) of the amyloid precursor protein (APP) and of its proteolytic fragments are still poorly understood. The secreted APPs ectodomain has been shown to be involved in neuroprotection and synaptic plasticity. The -secretase generated APP intracellular domain, AICD, functions as a transcriptional regulator in heterologous reporter assays although its role for endogenous gene regulation has remained controversial. Previously, we have generated APPs knockin (KI) mice expressing solely the secreted ectodomain APPs. Here, we generated double mutants (APPs-DM) by crossing APPs-KI mice onto an APLP2-deficient background and show that APPs rescues the postnatal lethality of the majority of APP/APLP2 double knockout mice. Despite normal CNS morphology and unaltered basal synaptic transmission, young APPs-DM mice already showed pronounced hippocampal dysfunction, impaired spatial learning and a deficit in LTP. To gain further mechanistic insight into which domains/proteolytic fragments are crucial for hippocampal APP/APLP2 mediated functions, we performed a DNA microarray transcriptome profiling of prefrontal cortex and hippocampus of adult APLP2-KO (APLP2-/-) and APPs-DM mice (APP/APLP2-/- mice).Interestingly, this analysis failed to reveal major genotype-related transcriptional differences. Expression differences between cortex and hippocampus were, however, readily detectable.
APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP.
Sex, Specimen part
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Exploiting microRNA and mRNA profiles generated in vitro from carcinogen-exposed primary mouse hepatocytes for predicting in vivo genotoxicity and carcinogenicity.
Specimen part, Compound
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrating factor analysis and a transgenic mouse model to reveal a peripheral blood predictor of breast tumors.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Experimentally derived metastasis gene expression profile predicts recurrence and death in patients with colon cancer.
Sex, Age, Disease stage, Race
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