Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established.
Assessing individual differences in genome-wide gene expression in human whole blood: reliability over four hours and stability over 10 months.
Sex, Age, Specimen part
View SamplesThe cholecystokinin B (2) receptor knockout (Cckbr KO) protects against allodynia induced by chronic constriction injury (CCI). The mechanism of this phenomenon is unknown, but must involve persistent changes in pain modulation and/or inflammatory pathways. We performed a gene expression study in two brain areas (midbrain and medulla) after surgical induction of CCI in Cckbr KO and wild-type (wt) control mice. The patterns of gene expression differences suggest that the immune system is activated in higher brain structures following CCI in the wt mice. The strongest differences include genes related to the MAPK pathway activation and cytokine production. In Cckbr KO mice this expressional pattern was absent. In addition, we found significant elevation of the Toll-like receptor 4 (Tlr4) in the supraspinal structures of the mice with deleted Cckbr compared to wt control mice. This up-regulation is most likely induced by the deletion of Cckbr. We suggest that there is a functional deficiency in the Tlr4 pathway which disables the development of neuropathic pain in Cckbr KO mice. Indeed, real time PCR analysis detected a CCI-induced upregulation of Tlr4 and Il1b expression in the lumbar region of wt but not Cckbr KO mice. Gene expression profiling indicates that elements of the immune response are not activated in Cckbr KO mice following CCI. Our findings suggest that there may be a role for CCK in the regulation of innate immunity.
Gene expression profiling reveals upregulation of Tlr4 receptors in Cckb receptor deficient mice.
No sample metadata fields
View SamplesWe used microarrays to determine the effect of prenatal nicotine exposure on gene expression profiles in the striatum of adolescent rats. We found a number of immediate early genes to be differentially expressed due to food-restriction.
Long-term effects of gestational nicotine exposure and food-restriction on gene expression in the striatum of adolescent rats.
Specimen part
View SamplesMouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression.
Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour.
No sample metadata fields
View SamplesPeroxisome proliferator-activated receptor alpha (PPAR) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPAR target gene in liver, but its function in hepatic lipid metabolism is unknown. We investigated the regulation of vanin-1, and total vanin activity, by PPAR in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPAR activity. In addition, activation of mouse PPAR regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPAR, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPAR agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. We show that hepatic vanin-1 is under extremely sensitive regulation by PPAR and that plasma vanin activity could serve as a readout of changes in PPAR activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting.
PPAR-alpha dependent regulation of vanin-1 mediates hepatic lipid metabolism.
Sex, Specimen part, Time
View SamplesMicroRNA-520f regulates EMT, as it activates CDH1 (mRNA) and E-cadherin (protein) expression, and it suppresses tumor cell invasion. We have characterized miR-520f target genes through whole genome transcriptional profiling of miRNA transfected pancreas cancer cells (PANC-1).
miRNA-520f Reverses Epithelial-to-Mesenchymal Transition by Targeting <i>ADAM9</i> and <i>TGFBR2</i>.
Cell line, Treatment
View SamplesThe aim of present study was to describe the genetic pathways activated during the community acquired bacterial meningitis (BM) by using genome-wide RNA expression profiling combined with functional annotation of transcriptional changes. We included 21 patients with BM hospitalized in 2008. The control group consisted of 18 healthy subjects. The RNA was extracted from whole blood, globin mRNA was depleted and gene expression profiling was performed with GeneChip Human Gene 1.0 ST Arrays enabling the analysis of 28,869 genes. Gene expression profile data were analyzed using Bioconductor packages and Bayesian modeling. Functional annotation of the enriched gene sets was used to define changed genetic networks. We also analyzed if the gene expression profile depends on the clinical course and outcome. In order to verify the genechip results, we chose ten functionally relevant genes with high statistical significance (CD177, IL1R2, IL18R1, IL18RAP, OLFM4, TLR5, CPA3, FCER1A, IL5RA, IL7R) and performed quantitative real-time (qRT) PCR.We identified the significant differences at p values of <0.05 in 8569 genes and after False Discovery Rate (FDR) correction, total of 5500 genes remained significant at p value of <0.01. Quantitative RT-PCR confirmed differential expression for selected genes. Functional annotation and network analysis indicated that most of the genes were related to activation of humoral and cellular immune responses (enrichment score 43). Those changes were found in adults and in children with BM compared to the healthy controls. Gene expression profile didnt depend on the clinical outcome, but there was very strong influence by the type of the pathogen. This study demonstrates a strong functional genomic evidence of the over-active immune response during bacterial meningitis. This hyperactive response possibly explains the complicated clinical course of this disease.
Peripheral blood RNA gene expression profiling in patients with bacterial meningitis.
Specimen part
View SamplesWFS1 gene is coding protein with unknown function but its functional deficiency causes different neuropsychiatric and neuroendocrine syndromes. In the present study we aimed to find the functional networks influenced by the Wfs1 deficiency in the hypothalamus. We performed gene expression profiling (Mouse Gene 1.0 ST Arrays) in Wfs1 deficient mice (ko). Modified t-statistics was used for comparison of groups (wt vs ko). Functional annotation of the alterations in RNA levels was performed with Ingenuity Pathway Analysis. 305 genes were differentially expressed with nominal p-value less than 0.01. FDR adjusted p-values were significant (0.007) only for two genes C4b (t=9.66) and Wfs1 (t=-9.03). However, several genes related to the G-protein signalling were very close to the FDR adjusted significance. For instance, Rgs4 (regulator of G-protein signalling 4) was down-regulated (-0.34, t=-5.4) in Wfs1 deficient mice. Changes in Rgs4 and C4B expression were confirmed by QRT-PCR. In humans, Rgs4 is in the locus for bipolar disease (BPD) and its expression is down-regulated in BPD. C4b is the gene related to the neurodegenerative diseases. In conclusion, hypothalamic gene expression profiling indicates alterations in some functionally relevant molecular pathways explaining the clinical syndrome in the Wolfram syndrome patients.
Hypothalamic gene expression profile indicates a reduction in G protein signaling in the Wfs1 mutant mice.
Specimen part
View SamplesAim of the present study was to compare the effect of chronic VPA treatment in wild type and Wfs1 knockout mice on hepatic gene expression profile.
Effect of chronic valproic Acid treatment on hepatic gene expression profile in wfs1 knockout mouse.
Sex, Specimen part
View SamplesCommunication between various ovarian cell types is a prerequisite for folliculogenesis and ovulation. In antral follicles granulosa cells divide into two distinct populations of mural (MGC) and cumulus granulosa cells (CGC), enveloping the antrum and surrounding the oocyte, respectively. IVF offers a good opportunity for analysing their functional properties since granulosa cells can be retrieved during the puncturing procedure of stimulated follicles. The aim of this study was to compare the transcriptomes of MGC and CGC in stimulated antral follicles obtained from 19 women undergoing IVF-ICSI procedure. MGC were obtained from follicular fluid and CGC were acquired after oocyte denudation for micromanipulation. Gene expression analysis was conducted using the genome-wide Affymetrix transcriptome array. The expression profile of the two granulosa cell populations varied significantly. Out of 28 869 analysed transcripts 4 480 were differentially expressed (q-value < 10-4) and 489 showed 2-fold difference in the expression level with 222 genes up-regulated in MGC and 267 in CGC. The transcriptome of MGC showed higher expression of genes involved in immune response, hematological system function and organismal injury, while CGC had genes involved in protein degradation and nervous system function up-regulated. Cell-to-cell signalling and interaction pathways were noted in both cell populations. Furthermore, numerous novel transcripts that have not been previously described in follicular physiology were identified. In conclusion, our results provide a solid basis for future studies in follicular biology that will help to identify molecular markers for oocyte and embryo viability in IVF.
The differential transcriptome and ontology profiles of floating and cumulus granulosa cells in stimulated human antral follicles.
Specimen part
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