Tmprss6 is the master inhibitor of hepcidin and its inactivation causes iron refractory iron deficiency anemia both in human and in mice. Mice with iron deficiency anemia (IDA)-low hepcidin show a pro-inflammatory response that is blunted in iron deficienct-high hepcidin Tmprss6 null mice. We investigated the transcriptional response associated with chronic hepcidin overexpression by comparing whole genome transcription profiling of the liver of Tmprss6 KO mice and IDA animals, irrespective of iron deficiency.
A strong anti-inflammatory signature revealed by liver transcription profiling of Tmprss6-/- mice.
Age, Specimen part
View SamplesThis experiment was carried out in the context of a pharmacogenetic study of long-term (4-year follow-up) response to Interferon-beta treatment in two cohorts of Italian Multiple Sclerosis patients, to identify genetic variants (SNPs) that may influence response to IFN-beta. We integrated results from meta-analysis of the two cohorts with gene expression profiling of IFN stimulated PBMCs from 20 healthy controls and eQTL analyses, to look at possible enrichment of IFN-beta induced genes with genes mapped by top-ranking meta-analyzed SNPs.
Pharmacogenetic study of long-term response to interferon-β treatment in multiple sclerosis.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesWe used RNA-Seq to compare transcriptomes of chemical reprogramming competent worms versus worms not competent for chemical reprogramming. We also performed RNA-seq during a time course of chemical reprogramming. Overall design: Three replicates of each of two reprogramming non-competent strains and three replicates of each of two reprogramming competent strains were collected. For the time course, five time points were analyzed (1, 2, 4, 6, and 18 hours) in either DMSO or DMSO + U0126 in three genotypes (non-reprogramming competent worms, reprogramming competent, and wildtype worms).
Competence for chemical reprogramming of sexual fate correlates with an intersexual molecular signature in Caenorhabditis elegans.
Subject
View SamplesYB-1 controls epithelial-mesenchymal transitions by restricting translation of growth-related mRNAs and enabling expression of EMT-inducing transcription factors. We used microarrays to characterize the direct transcriptional and indirect translational regulation of mRNAs by exogenous YB-1 in breast cancer cell lines.
Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.
No sample metadata fields
View SamplesThe nematode Caenorhabditis elegans is an important model for studies of germ cell biology, including specification as sperm or oocyte, the meiotic cell cycle and gamete differentiation. Fundamental to those studies is a genome-level knowledge of the germline transcriptome. Here we use RNA-Seq to identify genes expressed in isolated XX gonads, which are roughly 95% germline and 5% somatic gonadal tissue. We generate data from mutants making either sperm [fem-3(q96)] or oocytes (fog-2), both grown at 22°C. Our dataset identifies a total of 10,754 mRNAs in the polyadenylated transcriptome of XX gonads, with 1,723 enriched in spermatogenic gonads, 2,869 enriched in oogenic gonads and the remaining 6,274 not enriched in either. These spermatogenic, oogenic and gender-neutral gene datasets compare well with those of earlier studies, but double the number of genes identified. We also query our RNA-Seq data for differential exon usage and find 351 mRNAs with sex-specific isoforms. We suggest that this new dataset will prove useful for studies focusing on C. elegans germ cell biology. Overall design: Comparison of spermatogenic vs oogenic transcriptomes
A new dataset of spermatogenic vs. oogenic transcriptomes in the nematode Caenorhabditis elegans.
Specimen part, Cell line, Subject
View SamplesGlioblastoma multiforme (GBM) is a highly malignant primary central nervous neoplasm characterized by tumor cell invasion, robust angiogenesis, and a mean survival of 15 months. Human cytomegalovirus (HCMV) infection is present in > 90% of GBMs, although the role the virus plays in GBM pathogenesis is unclear. We report here that a majority of human GBM tumors express HCMV pp71, which has previously been found to promote cell cycle progression and viral replication, and that pp71 is expressed preferentially within the CD133+ cancer stem cell-like subpopulation. Overexpression of pp71 in adult neural precursor cells (NPCs) resulted in a dramatic induction of stem cell factor (SCF) gene expression, which has been identified as an important pro-angiogenic factor in GBM.
Cytomegalovirus pp71 protein is expressed in human glioblastoma and promotes pro-angiogenic signaling by activation of stem cell factor.
Cell line
View SamplesNovel prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit either markers of proliferation or of angiogenesis and mesenchyme. Analysis of gene expression data is described in Phillips et al., Cancer Cell, 2006.
Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.
Sex, Age, Disease stage
View SamplesPrimary glioma stem cells cultured as neurospheres in NBL media with growth factors were subjected to treatment with the non-toxic, non-psychoactive cannabis compound
Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.
Specimen part, Disease stage
View Samples5 arrays from obese insulin-resistant and lean insulin-sensitive females adipose tissue at fasting and after 3h hyperinsulinemia
Adipose tissue gene expression analysis reveals changes in inflammatory, mitochondrial respiratory and lipid metabolic pathways in obese insulin-resistant subjects.
Sex, Specimen part
View SamplesBackground: The vast majority of human genes (.70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. Methodology/Principal Findings: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. Conclusions/Significance: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatability gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF2 and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MGthymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse TranscriptionPolymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches
Identifying alternative hyper-splicing signatures in MG-thymoma by exon arrays.
Sex
View Samples