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SRP076218
Mus musculus
147 Downloadable Samples
Illumina HiSeq 2000
Description
The transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with the ß-blocker atenolol (ATE) and the ß-agonist isoproterenol (ISO). Differential expression analyses revealed a large set of genes responding to ISO (n=1770 at FDR=0.0001) and a comparatively small one responding to ATE (n=23 at FDR=0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation of r= -0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibited coherent transcription profiles across some strains and/or treatments. Correlations between such modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality. Our study provides new insights into the transcriptional response of the heart to perturbations of the ß-adrenergic system, implicating several new genes that had not been associated to this system previously. Overall design: Cardiac mRNA expression profiles of the various inbred mouse strains were examined either under baseline condition (control) or in response to chronic administration of isoproterenol or atenolol at 10 mg/kg per day for 2 weeks. Expression data were produced by RNA-sequencing, in triplicates, using the HiSeq 2000 Illumina platform. Only males, aged ten to twelve weeks on average, were included in the experimental protocol. Mouse ID numbers refer to those described in Berthonneche C. et al. PLoS One. 2009 Aug 12;4(8):e6610 (doi: 10.1371/journal.pone.0006610. PMID: 19672458). Corresponding individual phenotypic values, in particular heart rate, systolic blood pressure, electrocardiogaphic measurements and heart weight are available in dataset "maurer1" of the Mouse Phenome Database (http://phenome.jax.org/). Preparation of the sequencing libraries, RNA-sequencing and RNA expression quantitations were performed by the BGI.
Publication Title
RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: The basic helix-loop-helix transcription factor TWIST1 (Twist) is involved in embryonic cell lineage determination and mesodermal differentiation. There is evidence to indicate that Twist expression plays a role in breast tumor formation and metastasis, but the role of Twist in dysregulating pathways that drive the metastatic cascade is unclear. Importantly, the genes and pathways dysregulated by Twist in cell lines and mouse models have not been validated against data obtained from patient samples.
Publication Title
Genomic pathways modulated by Twist in breast cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Williams-Beuren Syndrome (WBS) is a neurodevelopmental disorder caused by aa 1.5 Mb microdeletion on human chromosome 7. Although the molecular cause of the disorder is well-established, little is known about the global impact of the deletion on gene expression. Here we profiled the transcriptomes of fibroblast cell lines from 8 young girls with WBS, and 9 sex- and age-matched control individuals
Publication Title
Using transcription modules to identify expression clusters perturbed in Williams-Beuren syndrome.
Sample Metadata Fields
Sex, Cell line
View Samples- 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- Caenorhabditis elegans
- 45 Downloadable Samples
- Illumina HiSeq 2500
Description
We conducted a time series of transcriptomics measurements during normal ageing in C. elegans in two non-reproductive strains (fem and gem) during normal ageing (days 1 to 10 of adulthood) and used this together with a multi-omics modelling pipeline to explore the changes that take place due to ageing. Overall design: Two strains and several time points with three replicates per strain and time point.
Publication Title
Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During <i>C. elegans</i> Aging.
Sample Metadata Fields
Age, Specimen part, Subject
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- Mus musculus
- 69 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
SCA1, a fatal neurodegenerative disorder, is caused by a CAG expansion encoding a polyglutamine stretch in the protein ATXN1. We used RNA-seq to profile cerebellar RNA expression in ATXN1 mice, including lines with ataxia and progressive pathology and lines having ataxia in absence of Purkinje cell progressive pathology. Weighted Gene Coexpression Network Analysis of the cerebellar RNA-seq data revealed two gene networks that significantly correlated with disease, the Magenta (342 genes) and Light Yellow (35 genes) Modules. Features of the Magenta and Light Yellow Modules indicate they reflect distinctive pathways. The Magenta Module provides a description of suppressed transcriptional programs reflecting disease progression in Purkinje cells, while the Lt Yellow Module reflects other transcriptional programs activated in response to disease in Purkinje cells as well as other cerebellar cell types. We also found that up-regulation of cholecystokinin (Cck) blocked progression of Purkinje cell pathology and that loss of Cck function in mice lacking progressive disease enabled Purkinje cell pathology to progress to cell death. Overall design: Cerebellar mRNA expression profiles from ATXN1[82Q], ATXN1[30Q], and ATXN1[30Q]-D776 transgenic mice and wild type/FVB mice at 5 weeks, 12 weeks and 28 weeks of age ---------------------------- cuffnorm_ATXN1.82Q_ATXN1.30Q.D776_WTFVB_genes.fpkm_tracking.txt: CuffNorm normalized values for all samples (snoRNAs and miRNAs removed) cuffdiff_week5_ATXN1.82Q_ATXN1.30Q.D776_WTFVB_gene_exp.diff.txt: Cuffdiff comparison between samples at week 5; pairwise comparisons between ATXN1[82Q], ATXN1[30Q]D776 and FVB cuffdiff_week12_ATXN1.82Q_ATXN1.30Q.D776_WTFVB_gene_exp.diff.txt: Cuffdiff comparison between samples at week 12; pairwise comparisons between ATXN1[82Q], ATXN1[30Q]D776 and FVB cuffdiff_week28_ATXN1.82Q_ATXN1.30Q.D776_WTFVB_gene_exp.diff.txt: Cuffdiff comparison between samples at week 28; pairwise comparisons between ATXN1[82Q], ATXN1[30Q]D776 and FVB cuffdiff_week5_vs_week12_vs_week28_ATXN1.82Q_gene_exp.diff.txt: Cuffdiff comparison between ATXN1[82Q] at week 5, week 12 and week 28 cuffdiff_week5_vs_week12_vs_week28_ATXN1.30Q.D776_gene_exp.diff.txt: Cuffdiff comparison between ATXN1[30Q]D776 at week 5, week 12 and week 28 cuffdiff_week5_vs_week12_vs_week28_FVB_gene_exp.diff.txt: Cuffdiff comparison between wt/FVB at week 5, week 12 and week 28
Publication Title
Cerebellar Transcriptome Profiles of ATXN1 Transgenic Mice Reveal SCA1 Disease Progression and Protection Pathways.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Arabidopsis thaliana
- 30 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We performed an analysis of transcriptomic responses to auxin within four distinct tissues of the Arabidopsis thaliana root. This high-resolution dataset shows how different cell types are predisposed to react to auxin with discrete transcriptional responses. The sensitivity provided by the analysis lies in the ability to detect cell-type specific responses diluted in organ-level analyses. This dataset provides a novel resource to examine how auxin, a widespread signal in plant development, influences differentiation and patterning in the plant through tissue-specific transcriptional regulation.
Publication Title
A map of cell type-specific auxin responses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
RNA sequencing (RNA-seq) analysis revealed 31 novel lncRNAs in HCASMC, including a vascular cell-enriched lncRNA called SENCR (for Smooth muscle and Endothelial cell long Non-Coding RNA). RT-PCR and hybridization studies show SENCR exists in two isoforms and is transcribed antisense from the 5’ end of the FLI1 gene. Knockdown of SENCR has no effect on FLI1 mRNA or protein expression. Biochemical fractionation and RNA fluorescence in situ hybridization (FISH) studies indicate SENCR is a cytoplasmic lncRNA. RNA-seq experiments in HCASMC where SENCR is attenuated disclose decreased expression of Myocardin and many SMC contractile genes; conversely a pro-migratory gene signature is increased. RT-PCR and Western blotting validated several differentially expressed genes following SENCR knockdown. Loss-of-function studies in scratch wound and Boyden chamber assays support SENCR as an inhibitor of vascular cell migration. Overall design: Total RNAs of 3 replicates of normal human coronary artery smooth muscle cells (Mock1, Mock2 and Mock3) were sequenced and analyzed for identification of novel lncRNAs. One of identified novel lncRNAs from that experiment is SENCR. To study its function, SENCR knock-down experiment were performed and then RNA-seq profiles of 3 replicates of both SENCR-knockdown samples and corresponding controls were compared.
Publication Title
Identification and initial functional characterization of a human vascular cell-enriched long noncoding RNA.
Sample Metadata Fields
No sample metadata fields
View Samples