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GSE40585
Homo sapiens
53 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The gene WFS1 encodes a protein with unknown function although its functional deficiency causes different neuropsychiatric and neuroendocrine syndromes. In the present study, we aimed to find the functional networks influenced by the time-dependent silencing of WFS1 in HEK cells. We performed whole genome gene expression profiling (Human Gene 1.0 ST Arrays) in HEK cells 24, 48, 72 and 96 hours after transfection with three different WFS1 siRNAs. In order to verify silencing we performed quantitative RT-PCR and western blot analysis. Analysis was conducted in two ways. First we analyzed the overall effect of the siRNA treatment on the gene expression profile. As a next step we performed time-course analysis separately for different siRNAs and combined for all siRNAs. Quantitative RT-PCR and western blot confirmed clear silencing of WFS1 gene expression after 48 hours. Eleven genes had an FDR value less than 10% and most of them were genes related to the mitochondrial dysfunction and apoptosis. Time-course analysis confirmed significant correlation between WFS1 silencing and changes in the expression profiles of several genes. The pathways that were influenced significantly by WFS1 silencing were related to mitochondrial damage and neurodegenerative diseases. Our findings suggest the role of WSF1 gene in cell survival and its involvement in the degenerative diseases.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Aim 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.
Publication Title
Effect of chronic valproic Acid treatment on hepatic gene expression profile in wfs1 knockout mouse.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Methcathinone (ephedrone) is relatively easily accessible for abuse. Its users develop an extrapyramidal syndrome and it is not known if this is caused by methcathinone itself, by side-ingredients (manganese), or both. In the present study we aimed to clarify molecular mechanisms underlying this condition. We used microarrays to analyze whole genome gene expression patterns of peripheral blood from 20 methcathinone users and 20 matched controls. Gene expression profile data were analyzed by Bayesian modelling and functional annotation. Of 28,869 genes on the microarrays, 326 showed statistically significant differential expression with FDR adjusted p-values below 0.05. Quantitative RT-PCR confirmed differential expression for the most of the genes selected for validation. Functional annotation and network analysis indicated activation of a gene network that included immunological disease, cellular movement and cardiovascular disease functions (enrichment score 42). As HIV and HCV infections were confounding factors, we performed additional stratification of patients. A similar functional activation of the immunological disease category was evident when we compared patients according to injection status (past versus current users, balanced for HIV and HCV infection). However, this difference was not large therefore the major effect was related to the HIV status of the patients. Mn-methcathinone abusers have blood RNA expression patterns that mostly reflect their HIV and HCV infections. However, despite the strong confounding effect from infection, some modest drug abuse effects on gene expression were detected.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The 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.
Publication Title
Peripheral blood RNA gene expression profiling in patients with bacterial meningitis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Communication 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.
Publication Title
The differential transcriptome and ontology profiles of floating and cumulus granulosa cells in stimulated human antral follicles.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 37 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Aim of present study was to describe the changes induced deletion of the Wfs1 gene in the temporal lobe of mice. Mutant mice were backcrossed to two different genomic backgrounds in order to exclude confounding foreign genomic background influence. Samples from temporal lobes were analyzed by using Affymetrix Genechips, expression profiles were functionally annotated by using GSEA and Ingenuity Pathway Analysis. We found that Wfs1 mutant mice are significantly smaller (20.9 1.6 g) than their wild-type counterparts (31.0 0.6g, p < 0.0001). Interestingly, genechip analysis identified growth hormone transcripts up-regulated and functional analysis found appropriate pathways activated. Moreover, we found significant increase in the level of IGF1 in the plasma of wfs1 mutant mice. Taken together, wfs1 mutation induces growth retardation whereas the growth hormone pathway is activated. Further studies are needed to describe biochemical and molecular details of the growth hormone axis in the wfs1 mutant mice.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The 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.
Publication Title
Gene expression profiling reveals upregulation of Tlr4 receptors in Cckb receptor deficient mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Oxidative damage contributes significantly to the pathogenesis of psoriasis. We recently developed antioxidative peptides (UPF peptides) activating the endogenous glutathione system (GSH). In the present study, we analyzed gene expression profiles in the samples of psoriasis patients to find if these peptides could reduce oxidative damage during psoriasis.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
WFS1 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.
Publication Title
Hypothalamic gene expression profile indicates a reduction in G protein signaling in the Wfs1 mutant mice.
Sample Metadata Fields
Specimen part
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