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GSE11967
Homo sapiens
8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Background: 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
Publication Title
Identifying alternative hyper-splicing signatures in MG-thymoma by exon arrays.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 29 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
PD is the second most common neurodegenerative disease worldwide with growing prevalence. MPTP is a neurotoxin which causes the appearance of Parkinson's disease (PD) pathology. The involvement of the cholinergic system in PD has been identified decades ago and anti-cholinergic drugs were upon the first drugs used for symptomatic treatment of PD. Of note, MPTP intoxication is a model of choice for symptomatic neuroprotective therapies since it have been quite predictive. Mice were exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP), with or without the protective acetylcholinesterase (AChE-R) variant. Transgenic AChE-S (the synaptic variant), AChE-R (the shorter, protective variant) and FVB/N control mice were included in this study. Two brain regions were examined: the pre-frontal cortex (PFC) and the striatal caudate-putamen (CPu). Each condition (i.e brain region and transgenic variant) was examined on both naive and MPTP-exposed mice.
Publication Title
Meta-analysis of genetic and environmental Parkinson's disease models reveals a common role of mitochondrial protection pathways.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Sub-thalamic deep brain stimulation (DBS) reversibly modulates Parkinsons disease (PD) motor symptoms, providing an unusual opportunity to compare leukocyte transcripts in the same subjects before and after neurosurgery and after disconnecting the stimulus (ON-and OFF-stimulus). Here, we report rapid stimulus-induced and largely reversible changes in PD leukocyte transcripts, which were larger in scope than the disease-induced changes. These transcript changes classified advanced pre- from post-surgery PD patients and discriminated patients from controls. Moreover, the extent of changes correlated with the neurological efficacy of the DBS neurosurgery, and covered both regulatory pathways and individual transcript changes, e.g. SNCA, PARK7 and the splicing factor SFRS1. Following 1 hour OFF-stimulus, these changes were largely reversed. We extracted from these differences a modified transcripts signature which discriminated controls from advanced PD patients, pre- from post-surgery and ON-from OFF-stimulus conditions. A further gene-list independent analysis detected reversed pathways. Our findings suggest future uses of this approach and the discovered molecular signature for early diagnostics of PD and for identifying novel targets for therapeutic intervention in this and other DBS-treatable neurological diseases.
Publication Title
Deep brain stimulation induces rapidly reversible transcript changes in Parkinson's leucocytes.
Sample Metadata Fields
Sex, Specimen part, Disease stage
View Samples- Homo sapiens
- 67 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Parkinsons Disease is a multi-system, disabling progressive neurodegenerative condition. Clinical progression is highly heterogeneous and, thus far, there are not available biomarkers to accurately predict the rate of disease progression. Thus, identifying molecular signatures that allow discriminating between different progression rates might significantly assist the therapeutic strategy, and enable improved outcomes in clinical trials.
Publication Title
Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles.
Sample Metadata Fields
Sex, Specimen part
View Samples- Arabidopsis thaliana
- 62 Downloadable Samples
Illumina HiSeq 2000
Description
RNAseq data for Col-0. cob-6, sfr6-3 and cob-6sfr6-3 Overall design: 7 days old seedlings grown in 24h light with 0
Publication Title
Identification of MEDIATOR16 as the Arabidopsis COBRA suppressor MONGOOSE1.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Mesio-Temporal Lobe Epilepsy (MTLE) syndrome is the most common form of intractable epilepsies. It is characterized by the recurrence of focal seizures occurring in mesio-temporal limbic structures and is often associated with hippocampal sclerosis and drug resistance.
Publication Title
Glial responses during epileptogenesis in Mus musculus point to potential therapeutic targets.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
YB-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.
Publication Title
Translational activation of snail1 and other developmentally regulated transcription factors by YB-1 promotes an epithelial-mesenchymal transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
AD is the leading cause of dementia in the elderly. However, disease etiology is still practically unknown. To gain insight into the molecular mechanisms underlying this disease we used the Affymetrix exon arrays to profile the alternative splicing landscape of human entorhinal cortex samples from AD patients and controls. We found a few hundred events of alternative spicing that characterize the AD entorhinal cortex and may have profound effect on the pathogenesis of this disease.
Publication Title
Cholinergic-associated loss of hnRNP-A/B in Alzheimer's disease impairs cortical splicing and cognitive function in mice.
Sample Metadata Fields
Age, Disease
View Samples- Arabidopsis thaliana
- 16 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Low oxygen stress dynamically regulates the translation of cellular mRNAs as a means of energy conservation in seedlings of Arabidopsis thaliana. Most of the highly hypoxia-induced mRNAs are recruited to polysomes and actively translated, whereas other cellular mRNAs become translationally inactive and are either targeted for stabilization or degradation. Here we identify the involvement of OLIGOURIDYLATE BINDING PROTEIN 1 (UBP1), a triple RNA Recognition Motif protein, in dynamic and reversible aggregation of translationally repressed mRNAs during hypoxia. Mutation or downregulation of UBP1C interferes with seedling establishment and reduces survival of low oxygen stress. By use of messenger ribonucleoprotein immunopurification, we show that UBP1C constitutively binds a subpopulation of mRNAs characterized by U-rich 3-untranslated regions under normoxic conditions. During hypoxia, UBP1C association with non-U-rich mRNAs is enhanced concomitant with its aggregation into microscopically visible cytoplasmic foci, referred to as UBP1 stress granules (SGs). This UBP1C-mRNA association occurs as global levels of protein synthesis decline. Upon reoxygenation, rapid UBP1 SG disaggregation coincides with the return of the stabilized mRNAs to polysomes. The mRNAs that are highly induced and translated during hypoxia largely circumvent UBP1C sequestration. Thus, UBP1 is established as a component of dynamically assembled cytoplasmic mRNPs that sequester mRNAs that are poorly translated during a transient low energy stress.
Publication Title
Selective mRNA sequestration by OLIGOURIDYLATE-BINDING PROTEIN 1 contributes to translational control during hypoxia in Arabidopsis.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- IlluminaHiSeq2000
Description
We sequenced total RNA from human monocyte derived macrophages (n = 6, healthy donors) pre-treated with calcineurin inhibitor FK506 (10 ng/ml) for 1h and stimulated with live Aspergillus fumigatus swollen conidia (MOI=1) for 1h and 6h. Overall design: We sequenced total RNA from human monocyte derived macrophages from six healthy donors. For each donor, we had six conditions (Unstimulated control, FK506 pre-treated control, 1 hour stimulation with live Aspergillus fumigatus, 1 hour stimulation with live Aspergillus fumigatus with FK506 pre-treatment, 6 hour stimulation with live Aspergillus fumigatus, 6 hour stimulation with live Aspergillus fumigatus with FK506 pre-treatment. In total we analysed 36 samples (6 healthy donors with 6 conditions).
Publication Title
Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death.
Sample Metadata Fields
No sample metadata fields
View Samples