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GSE46036
Mus musculus
7 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Peptide immunotherapy aims to specifically restore tolerance to the administered self-antigen and prevent autoimmunity without the perturbation of normal immune function. We have developed a dose escalation protocol for subcutaneous delivery of the MHC II-restricted myelin basic protein peptide analogue Ac1-9[4Y] to T cell receptor transgenic (Tg4) mice. Dose escalation allows safe administration of high doses of peptide, which effectively induces antigen-specific tolerance and suppresses the development of experimental autoimmune encephalomyelitis, a model for the human condition multiple sclerosis. CD4+ T cells isolated from treated mice are anergic and suppressive in vitro and respond to stimulation by secretion of the immunoregulatory cytokine IL-10. To understand the molecular changes occurring throughout the course of dose-escalation immunotherapy, we undertook microarray analysis of CD4+ T cells at different the stages of treatment, using Tg4 Rag-1 deficient mice, which lack naturally occurring regulatory T cells and have a monoclonal CD4+ T cell population
Publication Title
Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Human cytomegalovirus induces a pro-inflammatory monocyte following infection. To begin to address how HCMV induces these rapid changes in infected monocytes, we examined the transcriptome of infected monocytes. Global transcriptional profiling using cDNA microarrays revealed a significant number of pro-inflammatory genes were upregulated within 4 hours post infection.
Publication Title
Transcriptome analysis reveals human cytomegalovirus reprograms monocyte differentiation toward an M1 macrophage.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 168 Downloadable Samples
Illumina HiSeq 2500
Description
Adult zebrafish are capable of regenerating cardiac tissue following ventricular resection within 30 days. We profiled both small RNA and mRNA expression in uninjured (0dpa), 1, 3, 7, 14, 21 and 30 days post amputation to study biological processes orchestrate each stage of regeneration. Overall design: Small and mRNA gene expression profiling during 0, 1, 3, 7, 14, 21 and 30 days post ventricular resection.
Publication Title
RegenDbase: a comparative database of noncoding RNA regulation of tissue regeneration circuits across multiple taxa.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The chronological lifespan (CLS) of Saccharomyces cerevisiae is defined as the number days that non-dividing cells remain viable, typically in stationary phase cultures or in water. CLS is extended by restricting glucose in the starting cultures, and is considered a form of caloric restriction (CR). Through a previous genetic screen our lab determined that deleting components of the de novo purine biosynthesis pathway also significantly increased CLS. Significant similarities in gene expression profiles between calorie restricted WT cells and a non-restricted ade4 mutant suggested the possibility of common gene expression biomarkers of all chronologically long lived cells that could also provide insights into general mechanisms of lifespan extension. We have identified additional growth conditions that extend CLS of WT cells, including supplementation of the media with isonicotinamide (INAM), a known sirtuin activator, or by supplementation with a concentrate collected from the expired media of a calorie restricted yeast culture, presumably due to an as yet unidentified longevity factor. Using these varied methods to extend CLS, we compared gene expression profiles in the aging cells (at day 8) to identify functionally relevant biomarkers of longevity. Nineteen genes were differentially regulated in all 4 of the long-lived populations relative to wild type. Of these 19 genes, viable haploid deletion mutants were available for 16 of them, and 12 were found to have a significant impact on CLS.
Publication Title
Functional genomic analysis reveals overlapping and distinct features of chronologically long-lived yeast populations.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bromodomain-containing proteins bind acetylated lysine residues on histone tails and are involved in the recruitment of additional factors that mediate histone modifications and enable transcription. A compound, I-BET-762, that inhibits binding of an acetylated histone peptide to BRD4 and other proteins of the BET (bromodomain and extra-terminal domain) family, was previously shown to suppress the production of pro-inflammatory proteins by macrophages and block acute inflammation in mice. Here we investigate the effect of I-BET-762 on T cell function. We show that treatment of nave CD4+ T cells with I-BET-762 during early differentiation modulates subsequent cytokine production, and inhibits the ability of Th1-skewed cells to induce autoimmune pathogenesis in a model of experimental autoimmune encephalomyelitis (EAE) in vivo. The suppressive effects of I-BET-762 on T-cell mediated inflammation were not due to inhibition of expression of the pro-inflammatory cytokines, IFN-. or IL-17, but correlated with the ability to suppress GM-CSF production from CNS-infiltrating T cells, resulting in decreased recruitment of macrophages and granulocytes. The effects of I-BET-762 were distinct from those of the fumarate ester, dimethyl fumarate (DMF), a candidate drug for treatment of multiple sclerosis (MS). Our data suggest that I-BET and DMF could have complementary roles in the treatment of MS, and provide a strong rationale for inhibitors of BET-family proteins in the treatment of autoimmune diseases, based on their dual ability to suppress granulocyte and macrophage recruitment by T cells as well as production of pro-inflammatory proteins by macrophages.
Publication Title
Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Studies investigating the causes of autism spectrum disorder (ASD) point to genetic as well as epigenetic mechanisms of the disease. Identification of epigenetic processes that contribute to ASD development and progression is of major importance and may lead to the development of novel therapeutic strategies. Here we identify the bromodomain and extra-terminal domain containing transcriptional regulators (BETs) as epigenetic drivers of an ASD-like disorder in mice. We found that the pharmacological suppression of the BET proteins by a novel, highly selective and brain-permeable inhibitor, I-BET858, leads to selective suppression of neuronal gene expression followed by the development of an autism-like syndrome in mice. Many of the I-BET858 affected genes have been linked to ASD in humans thus suggesting the key role of the BET-controlled gene network in ASD. Our studies also suggest that environmental factors controlling BET proteins or their target genes may contribute to the epigenetic mechanism of ASD.
Publication Title
Autism-like syndrome is induced by pharmacological suppression of BET proteins in young mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We investigated the anti-leukemic effects of the Bromodomain and Extra Terminal inhibitor I-BET151 on primary MLL-AF4 patient samples, using a xenotransplantation mouse model of MLL+ infant ALL in vivo. We reported that I-BET151 treatment impairs the engraftment and the disease burden of primary MLL+ infant ALL samples transplanted into immunedeficient mice. I-BET151 is able to arrest the growth of leukemic cells by blocking cell division and rapidly inducing apoptosis, through the deregulation of crucial target genes of the BRD4 and HOXA9/HOXA7 network. Moreover I-BET151 sensitizes glucocorticoid-resistant MLL+ cells to Prednisolone. Finally we observed that I-BET151 treatment is even more efficient when used in combination with HDAC inhibitor.
Publication Title
Antileukemic Efficacy of BET Inhibitor in a Preclinical Mouse Model of MLL-AF4<sup>+</sup> Infant ALL.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 282 Downloadable Samples
- Illumina HiSeq 2000
Description
Previous studies had shown that integration of genome wide expression profiles, in metabolic tissues, with genetic and phenotypic variance, provided valuable insight into the underlying molecular mechanisms. We used RNA-Seq to characterize hypothalamic transcriptome in 99 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP), a reference resource population for cardiovascular and metabolic traits. We report numerous novel transcripts supported by proteomic analyses, as well as novel non coding RNAs. High resolution genetic mapping of transcript levels in HMDP, reveals both local and trans expression Quantitative Trait Loci (eQTLs) demonstrating 2 trans eQTL "hotspots" associated with expression of hundreds of genes. We also report thousands of alternative splicing events regulated by genetic variants. Finally, comparison with about 150 metabolic and cardiovascular traits revealed many highly significant associations. Our data provides a rich resource for understanding the many physiologic functions mediated by the hypothalamus and their genetic regulation. Overall design: 282 samples, 3 biological replicates per strain
Publication Title
Hypothalamic transcriptomes of 99 mouse strains reveal trans eQTL hotspots, splicing QTLs and novel non-coding genes.
Sample Metadata Fields
Sex, Cell line, Subject
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HiSeq 2500
Description
We decribe the accessible chormatin landscape in RAS-induced (RIS) and NOTCH induced senescence (NIS) using ATAC-seq. By expressing active NOTCH (N1ICD) in the context of RIS, we find that N1ICD antagonises the formation of accessible regions in RIS. By performing co-cultures, we demonstrate that cells expressing a NOTCH1 ligand, JAGGED1, can antagonise the formation of RIS specific accessible regions. Overall design: mRNA profiles were IMR90 cells expressing ER:HRAS(G12V) and a control vector or MSCV miR30 shHMGA1 were generated. 6 biological replicates.
Publication Title
NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 151 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Human rhinoviruses (HRV) are among the most common causes of respiratory infections in humans but can be frequently detected also in asymptomatic subjects. We evaluated the value of gene expression profiles to differentiate asymptomatic detection from symptomatic HRV infection in children.
Publication Title
Rhinovirus Detection in Symptomatic and Asymptomatic Children: Value of Host Transcriptome Analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Race
View Samples