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GSE59860
Homo sapiens
17 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st), Illumina Genome Analyzer IIx
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 17 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st), Illumina Genome Analyzer IIx
Description
Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human nave and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between nave and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to nave cells, revealing specific genes more rapidly expressed in memory compared to nave cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression.
Publication Title
Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Memory T cells are primed for rapid responses to antigen; however, the molecular mechanisms responsible for priming remain incompletely defined. CpG methylation in promoters is an epigenetic modification, which regulates gene transcription. Using targeted bisulfite sequencing, we examined methylation of 2100 genes (56,000 CpG) mapped by deep sequencing to T cell activation in human naïve and memory CD4 T cells. 466 CpGs (132 genes) displayed differential methylation between naïve and memory cells. 21 genes exhibited both differential methylation and gene expression before activation, linking promoter DNA methylation states to gene regulation; 6 genes encode proteins closely studied in T cells while 15 genes represent novel targets for further study. 39 genes exhibited reduced methylation in memory cells coupled with increased gene expression with activation compared to naïve cells, revealing specific genes more rapidly expressed in memory compared to naïve cells and potentially regulated by DNA methylation. These findings define a DNA methylation signature unique to memory CD4 T cells and correlated with activation-induced gene expression. Overall design: RNA sequencing of primary human naïve and memory CD4 T cells at rest and 48 hours post-activation.
Publication Title
Defining CD4 T cell memory by the epigenetic landscape of CpG DNA methylation.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Host pathways mediating changes in immune states elicited by intestinal microbial colonization are incompletely characterized. Here we describe alterations of the host immune state induced by colonization of germ-free zebrafish larvae with an intestinal microbial community or single bacterial species. We show that microbiota-induced changes in intestinal leukocyte subsets and whole-body host gene expression are dependent on the innate immune adaptor gene myd88. Similar patterns of gene expression are elicited by colonization with conventional microbiome, as well as mono-colonization with two different zebrafish commensal bacterial strains. By studying loss-of-function myd88 mutants, we find that colonization suppresses Myd88 at the mRNA level. Tlr2 is essential for microbiota-induced effects on myd88 transcription and intestinal immune cell composition. Overall design: Zebrafish embryos were sterilized to generate germ-free groups. Transcriptomic responses in germ-free embryos were were assessed relative to colonized embryos, either colonized by complex and in characterized microbial communities (Conventionalozation) or by specefic single commensal bacterial species (monoassociation, Exiguobacterium/Chryseobacterium)
Publication Title
Intestinal microbiome adjusts the innate immune setpoint during colonization through negative regulation of MyD88.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Two genes have a synthetic lethal relationship when silencing or inhibition of one gene is only lethal in the context of a mutation or activation of the second gene. This situation offers an attractive therapeutic strategy, as inhibition of such a gene will only trigger cell death in tumor cells with an activated second oncogene but spare normal cells without activation of the second oncogene. Here we present evidence that CDK2 is synthetic lethal to neuroblastoma cells with MYCN amplification and overexpression. Neuroblastomas are childhood tumors with an often lethal outcome. Twenty percent of the tumors have MYCN amplification and these tumors are ultimately refractory to any therapy. Targeted silencing of CDK2 by three RNA interference techniques induced apoptosis in MYCN-amplified neuroblastoma cell lines, but not in MYCN single copy cells. Silencing of MYCN abrogated this apoptotic response in MYCN-amplified cells. Inversely, silencing of CDK2 in MYCN single copy cells did not trigger apoptosis, unless a MYCN transgene was activated. The MYCN induced apoptosis after CDK2 silencing was accompanied by nuclear stabilization of P53 and mRNA profiling showed up-regulation of P53 target genes. Silencing of P53 rescued the cells from MYCN-driven apoptosis. The synthetic lethality of CDK2 silencing in MYCN activated neuroblastoma cells can also be triggered by inhibition of CDK2 with a small molecule drug. Treatment of neuroblastoma cells with Roscovitine, a CDK inhibitor, at clinically achievable concentrations induced MYCN-dependent apoptosis. The synthetic lethal relation between CDK2 and MYCN indicates CDK2 inhibitors as potential MYCN-selective cancer therapeutics.
Publication Title
Inactivation of CDK2 is synthetically lethal to MYCN over-expressing cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
To seek whether seasonal variation in environmental particulate matter composition affected the global gene response patterns in cultured human cells representing pulmonary and systemic vascular targets.
Publication Title
Comparative gene responses to collected ambient particles in vitro: endothelial responses.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 18 Downloadable Samples
- Illumina HiSeq 3000
Description
ZIP-3 has been shown to repress the mitochondrial-UPR response. To identify genes repressed by ZIP-3, we compared transcript profiles from wildtype, atfs-1(tm4919) and zip-3(gk3164) worms raised on control RNAi or spg-7 RNAi Overall design: RNA samples were prepared from wild-type(wt) and zip-3(gk3164)(mutant) worms fed either control RNAi or spg-7 RNAi. Worms were synchronized by bleaching, raised on NGM plates seeded with control RNAi or spg-7 RNAi till L4 stage and then harvested. Each experiment was performed in triplicate indicated as 1,2 and 3.
Publication Title
Mitochondrial UPR repression during <i>Pseudomonas aeruginosa</i> infection requires the bZIP protein ZIP-3.
Sample Metadata Fields
Specimen part, Subject
View Samples- Caenorhabditis elegans
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
ZIP-3 has been shown to repress the mitochondrial-UPR genes and immune response during P. aeruginosa infection. To identify genes repressed by ZIP-3, we compared transcript profiles from wildtype and zip-3(gk3164) worms raised on P. aeruginosa or E. coli. Overall design: RNA samples were prepared from wild-type(wt) and zip-3(gk3164)(mutant) worms fed either E. coli or P. aeruginosa. Worms were synchronized by bleaching, starved on empty NGM plates for 48h, transferred to E. coli or P. aeruginosa seeded NGM plates for 18h and then harvested. Each experiment was performed in triplicate indicated as 1,2 and 3.
Publication Title
Mitochondrial UPR repression during <i>Pseudomonas aeruginosa</i> infection requires the bZIP protein ZIP-3.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Small molecule splicing modifiers have been extensively described which target the generic splicing machinery and thus have low target specificity. We have identified potent splicing modifiers with unprecedented high selectively, correcting the splicing deficit of the SMN2 (survival motor neuron 2) gene in Spinal Muscular Atrophy (SMA). Here we show that they directly bind to two sites of the SMN2 pre-mRNA, thereby stabilizing a novel ribonucleoprotein (RNP) complex in the SMN2 gene that is critical for the high target specificity of these small molecules over other genes. In addition to the therapeutic potential of these molecules for treatment of SMA, our work may have wide-ranging consequences for further research to identify small molecules that target splicing correction of specific genes by interacting with tertiary RNA structures. Overall design: mRNA profiling of type I SMA fibroblasts treated with NVS-SM1
Publication Title
Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiles were assessed for vincristine-sensitive parental ovarian tumor cell line (SKOV3) and its highly vincristine-resistant derivative (SKVCR 2.0)
Publication Title
Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples