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GSE27962
Sus scrofa
16 Downloadable Samples
Affymetrix Porcine Genome Array (porcine)
Description
The molecular mechanism underlying cardiac remodeling following myocardial infarction have been incompletely understood. Until now, most studies have been performed in rodents. We studied cardiac remodeling in the physiologically more relevant animal model, the swine.
Publication Title
Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Constitutive activation of the Wnt pathway leads to adenoma formation, an obligatory step towards intestinal cancer. In view of the established role of Wnt in regulating stemness, we attempted the isolation of cancer stem cells (CSCs) from Apc- and Apc/KRAS-mutant intestinal tumours. Whereas CSCs are present in malignant Apc/KRASmutant carcinomas, they appear to be very rare (<10-6) in the benign Apcmutant adenomas. In contrast, the Lin-CD24hiCD29+ subpopulation of adenocarcinoma cells appear to be enriched in CSCs with increased levels of active -catenin. Expression profiling analysis of the CSC-enriched subpopulation confirmed their enhanced Wnt activity and revealed additional differential expression of other signalling pathways, growth factor binding proteins, and extracellular matrix components. As expected, genes characteristic of the Paneth cell lineage (e.g. defensins) are co-expressed together with stem cell genes (e.g. Lgr5) within the CSC-enriched subpopulation. This is of interest as it may indicate a cancer stem cell niche role for tumor-derived Paneth-like cells, similar to their role in supporting Lgr5+ stem cells in the normal intestinal crypt. Overall, our results indicate that oncogenic KRAS activation in Apc-driven tumours results in the expansion of the CSCs compartment by increasing b-catenin intracellular stabilization.
Publication Title
Cancer stemness in Apc- vs. Apc/KRAS-driven intestinal tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
With the goal of specifically dissecting the toxicogenomic signatures of the helper-dependent (HD) human (HAd5) and canine (CAV-2) adenovirus, the VSV-G-pseudotyped SIN HIV-1 (LV) and the Adenoviral-associated vector 2/9 for human neurons (AAV2/9), we transduced a bona fide human neuronal system with HD-HAd5, HD-CAV-2, LV and AAV2/9, we analysed the transcriptional response of more than 47,000 transcripts using gene chips.
Publication Title
Differentiated neuroprogenitor cells incubated with human or canine adenovirus, or lentiviral vectors have distinct transcriptome profiles.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Brain gene transfer using viral vectors will likely become a therapeutic option for several disorders. Helper-dependent (HD) canine adenovirus type 2 vectors (CAV-2) are well suited for this goal. Indeed, these vectors are poorly immunogenic, efficiently transduce neurons, are retrogradely transported to afferent structures in the brain, and lead to long-term transgene expression. CAV-2 vectors have been exploited to unravel behavior, cognition, neural networks, axonal transport and therapy for orphan diseases. Here we describe the HD-CAV-2 vector induced transcriptional response of human dopaminergic neurospheres derived from midbrain progenitors. In this 3D model system, brain cell functions and dynamics mimic several aspects the dynamic nature of human brain. With the goal of better understanding and characterizing HD CAV-2 for brain therapy, we analyzed the transcriptomic modulation induced by HD-CAV-2 in this brain model system.
Publication Title
Transcriptional Response of Human Neurospheres to Helper-Dependent CAV-2 Vectors Involves the Modulation of DNA Damage Response, Microtubule and Centromere Gene Groups.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Objective: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), characterized by a global increasing incidence driven by relapsing-remitting disease in females. p38 MAP kinase (MAPK) has been described as a key regulator of inflammatory responses in autoimmunity, but its role in the sexual dimorphism in MS or MS models remains unexplored. Methods: Toward this end, we used experimental autoimmune encephalomyelitis (EAE), the principal animal model of MS, combined with pharmacologic and genetic inhibition of p38 MAPK activity and transcriptomic analyses. Results: Pharmacologic inhibition of p38 MAPK selectively ameliorated EAE in female mice. Conditional deletion studies demonstrated that p38 signaling in macrophages/myeloid cells, but not T cells or dendritic cells, recapitulated this sexual dimorphism. Analysis of CNS inflammatory infiltrates showed that female, but not male mice lacking p38 in myeloid cells exhibited reduced immune cell activation compared with controls, while peripheral T cell priming was unaffected in both sexes. Transcriptomic analyses of myeloid cells revealed differences in p38-controlled transcripts comprising female- and male-specific gene modules, with greater p38 dependence of pro-inflammatory gene expression in females. Interpretation: Our findings demonstrate a key role for p38 in myeloid cells in CNS autoimmunity and uncover important molecular mechanisms underlying sex differences in disease pathogenesis. Taken together, our results suggest that the p38 MAPK signaling pathway represents a novel target for much needed disease modifying therapies for MS
Publication Title
Sex-specific control of central nervous system autoimmunity by p38 mitogen-activated protein kinase signaling in myeloid cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 78 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This study sought correlates of relapse tendency in TTP by examining gene expression profiles in peripheral blood leukocytes from patients with acquired ADAMTS13-deficient TTP in remission and matched healthy controls for global gene expression and autoantibodies.
Publication Title
Ribosomal and immune transcripts associate with relapse in acquired ADAMTS13-deficient thrombotic thrombocytopenic purpura.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Understanding the DNA elements that constitute and control the regulatory genome is critical for the appropriate therapeutic management of complex diseases. Here, using chromosome Y (ChrY) consomic mouse strains on the C57BL/6J background, we show that susceptibility to two diverse animal models of autoimmune disease, including experimental allergic encephalomyelitis (EAE) and experimental myocarditis, correlates with the natural variation in copy number of Sly and Rbmy multicopy ChrY genes. In the B6 background, ChrY possesses gene regulatory properties that impact both genome-wide gene expression and the presence of alternative splice variants in pathogenic CD4+ T cells. Using a ChrY consomic strain on the SJL background, we discovered a preference for ChrY-mediated gene regulation in macrophages, the immune cell subset underlying the EAE sexual dimorphism in SJL mice, rather than CD4+ T cells. Importantly, in both genetic backgrounds, an inverse correlation exists between the number of Sly and Rbmy ChrY gene copies and the number of significantly upregulated genes in immune cells, thereby supporting a link between copy number variation of Sly and Rbmy with the ChrY genetic element exerting regulatory properties. Moreover, in humans, an analysis of the CD4+ T cell transcriptome from male multiple sclerosis patients versus healthy controls provides further evidence for an evolutionarily conserved mechanism of gene regulation by ChrY. Thus, these data establish ChrY as a member of the regulatory genome in mammals due to its ability to regulate gene expression and alternative splicing in immune cells linked to disease.
Publication Title
The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alveolar macrophages from never smokers and active smokers were isolated by bronchoalveolar lavage and gene expression was measured. Chronic cigarette smoke exposure, as occurs in smoker's lungs, leads to significant changes in gene expression. Of note, RNA was isolated immediately following bronchoscopy. Alveolar macrophage levels were >95%.
Publication Title
Cigarette smoking decreases global microRNA expression in human alveolar macrophages.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Understanding the DNA elements that constitute and control the regulatory genome is critical for the appropriate therapeutic management of complex diseases. Here, using chromosome Y (ChrY) consomic mouse strains on the C57BL/6J background, we show that susceptibility to two diverse animal models of autoimmune disease, including experimental allergic encephalomyelitis (EAE) and experimental myocarditis, correlates with the natural variation in copy number of Sly and Rbmy multicopy ChrY genes. In the B6 background, ChrY possesses gene regulatory properties that impact both genome-wide gene expression and the presence of alternative splice variants in pathogenic CD4+ T cells compared to CD4+ T cells. An inverse correlation exists between the number of Sly and Rbmy ChrY gene copies and the number of significantly upregulated genes in immune cells, thereby supporting a link between copy number variation of Sly and Rbmy and the ChrY genetic element exerting regulatory properties. Thus, these data establish ChrY as a member of the regulatory genome in mammals due to its ability to regulate gene expression and alternative splicing in immune cells linked to disease.
Publication Title
The Y chromosome as a regulatory element shaping immune cell transcriptomes and susceptibility to autoimmune disease.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples