Ataxin 1 (Atxn1) is a protein of unknown function associated with cerebellar neurodegeneration in spinocerebellar ataxia type 1 (SCA1). SCA1 is caused by an expanded polyglutamine within Atxn1 by gain-of-function mechanisms. Lack of Atxn1 in mice triggers motor deficits in the absence of neurodegeneration or apparent neuropathological abnormalities.We extracted RNA from cerebellum of 5 Atxn1-null mice and 5 WT. Cerebellar gene expression profiles at 15 weeks of age were generated usSCA1 ing Affymetrix MOE430A arrays. Identifying the molecular pathways regulated by Atxn1 can provide insights into the early molecular mechanisms underlying neuronal dysfunction.
Down-regulation of the dopamine receptor D2 in mice lacking ataxin 1.
Age, Specimen part
View SamplesThe purpose of the experiment was to generate a time course of gene expression following irradiation. The goal was then to model this data to extract hidden variables - chiefly, the activity profiles of the p53 transcription factor. Using this information the aim was to predict which transcripts changed by IR were targets of p53. Cells in log phase (1 x 106 ml-1) were ?-irradiated with 5 Gy at room temperature (RT) at a dose rate of 2.45 Gy per minute with a 137Cs ?-irradiator. Cells were harvested at 0, 2, 4, 6, 8, 10 and 12 hours, and RNA and protein were extracted (Trizol, Invitrogen). Affymetrix U133A arrays were hybridized as standard (www.affymetrix.co.uk). Array quality was determined using R and GCOS .rpt file values. The time course was replicated three times from independent cell preparations.
Ranked prediction of p53 targets using hidden variable dynamic modeling.
Specimen part, Disease, Cell line, Time
View SamplesChromatin remodelling provides a key mechanism for the regulation of gene expression through dynamic alterations in nucleosome occupancy at promoters and enhancers. Haploinsufficiency for the ATP-dependent chromatin remodeller chromodomain-helicase-DNA-binding protein 7 (CHD7) causes human CHARGE syndrome. CHARGE is characterised by a distinct pattern of congenital anomalies, including cardiovascular malformations, and has traditionally been considered a neurocristopathy. We present a new perspective, by showing severe structural cardiovascular defects following ablation of Chd7 in the anterior mesoderm and other cardiac-related lineages. We identify multiple downstream pathways affected by the loss of Chd7 and disruption of excitation-contraction coupling in cardiomyocytes. Furthermore, we demonstrate CHD7 binding at the Sema3C promoter and alterations to the local chromatin structure in vivo, indicating direct transcriptional regulation. This work therefore provides novel insights into the etiology of heart defects arising in CHARGE syndrome and reveals a requirement for CHD7 activity in mesodermal cardiac progenitors.
A critical role for the chromatin remodeller CHD7 in anterior mesoderm during cardiovascular development.
Specimen part
View SamplesIn the context of T1 Diabetes, pro-inflammatory cytokines IL-1 and IFN- are known to contribute to -cell apoptosis;
Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference.
Specimen part, Treatment, Time
View SamplesIn the context of T1 Diabetes, pro-inflammatory cytokines IL-1 and IFN- are known to contribute to -cell apoptosis;
Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference.
Cell line, Treatment, Time
View SamplesT-cell replete cord blood transplantation results in a rapid thymus-independent T-cell reconstitution which is strikingly CD4+ biased compared to the well-established observation of CD8+ T-cell biased expansion after T-cell replete bone marrow transplant.
No associated publication
Age, Specimen part
View SamplesGene expression on peripheral blood mononuclear cells (PBMC) from SPARKS CHARMS juvenile idiopathic arthritis (JIA) cohort pre and post methotrexate therapy. This is the first study to our knowledge, to evaluate gene expression profiles in children with JIA before and after MTX, and to analyze genetic variation in differentially expressed genes. We have identified a gene, which may contribute to genetic variability in MTX response in JIA.
Generation of novel pharmacogenomic candidates in response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype.
Specimen part, Treatment, Subject
View SamplesChildren with oligoarticular JIA (arthritis in 4 or fewer joints) can either continue to have this mild form of arthritis (persistent oligoarticular JIA) or extend to a more sever form involving more than 4 joints (extended oligoarticular JIA)
Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expression.
Specimen part
View SamplesSF-1 (NR5A1) was overexpressed (Over) or knocked down with shRNA (shRNA) in NCI-H295R human adrenocortical tumor cells and differential global gene expression analysed 48 hours later using Affymetrix GeneChip Human Gene 1.0ST arrays. Over: 5 million cells were transfected (Amaxa Nucleofection) with 10 ug of a pIRES2-AcGPF1-Nuc construct co-expressing SF-1 cDNA and GFP. For experimental control, a mutagenized pIRES2 construct, bearing the G35E mutation in SF-1 that impairs its transactivation function in vivo and in vitro was used. shRNA: 5 million cells were transfected (Amaxa Nucleofection) with 10 ug of the SureSilencing shRNA Plasmid for Human NR5A1 with GFP marker kit (SABioscience). For experimental control, mismatch constructs provided in the kit were used. In both experiments (Over and shRNA), cells were harvested, prepared, and submitted to fluorescence-activated cell sorting (FACS) in a MoFlo XDP sorter 48 hours after transfection. Viable GFP-expressing cells were pooled and resuspended in TRIzol reagent for RNA extraction. Total RNA was extracted, and RNA quality control performed using a 2100 Bioanalyzer.
No associated publication
Disease, Cell line
View SamplesWe hypothesised that neutrophil pathways could be also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab.
No associated publication
Specimen part, Disease, Disease stage
View Samples