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Mus musculus
15 Downloadable Samples
NextSeq 500
Description
Patients deficient in the guanine nucleotide exchange factor DOCK8 have decreased numbers and impaired in vitro function of T regulatory (Treg) cells and make autoantibodies, but seldom develop autoimmunity. We show that similarly, Dock8-/- mice have decreased numbers and impaired in vitrofunction of Treg cells, but do not develop autoimmunity. In contrast, mice with selective DOCK8 deficiency in Treg cells develop lymphoproliferation, autoantibodies, and gastrointestinal inflammation, despite normal percentage and in vitro function of Treg cells, suggesting that deficient T effector cell function might protect DOCK8 deficient patients from autoimmunity. We demonstrate that DOCK8 associates with STAT5 and is important for IL-2 driven STAT5 phosphorylation in Treg cells. DOCK8 localizes within the lamellar actin ring of the Treg cell immune synapse (IS). Dock8-/- Treg cells have abnormal TCR-driven actin dynamics, decreased adhesiveness, altered gene expression profile, an unstable IS with decreased recruitment of signaling molecules, and impaired transendocytosis of the co-stimulatory molecule CD86. These data suggest that DOCK8 enforces immunological tolerance by promoting IL-2 signaling, TCR-driven actin dynamics, and the IS in Treg cells. Overall design: CD4+CD25+CD39+YFP+ and CD4+CD25+CD39+YFP- Treg cells were isolated from the spleen and lymph nodes of Foxp3YFP-Cre/+/Dock8flox/flox mice. Treg cells were then cultured overnight in complete media alone or in the presence of media + anti-CD3+CD28 beads (1 bead per cell). After 16 hours, cells were harvested and the RNA was isolated. For unstimulated samples, there were 4 independent YFP- samples and 6 independent YFP+ samples. For bead stimulated samples, there were 3 independent YFP- samples and 2 YFP+ samples.
Publication Title
DOCK8 enforces immunological tolerance by promoting IL-2 signaling and immune synapse formation in Tregs.
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Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Arabidopsis thaliana
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Seed development is sensitive to parental dosage, with excess maternal or paternal genomes creating reciprocal phenotypes. Paternal genomic excess results in extensive endosperm proliferation without cellularization and eventual seed abortion. We previously showed that loss of the RNA POL IV gene nrpd1 in tetraploid fathers represses seed abortion in paternal excess crosses. Here we show genetically that RNA-directed DNA methylation (RdDM) pathway activity in the paternal parent is sufficient to determine the viability of paternal excess seeds. The status of the RdDM pathway in paternal excess endosperm does not impact seed viability. Comparison of endosperm transcriptomes, DNA methylation, and small RNAs from balanced and paternal excess endosperm demonstrates that paternal excess seed abortion is unlikely to be dependent on either transposable element or imprinted gene mis-regulation. We suggest instead that loss of paternal RdDM modulates expression at a small subset of genes and desensitizes endosperm to paternal excess. Finally, using allele-specific transcription data, we present evidence of a transcriptional buffering system that up37 regulates maternal alleles and represses paternal alleles in response to excess paternal genomic dosage. These findings prompt reconsideration of models for dosage sensitivity in endosperm. Overall design: Examination of parent-of-origin specific and total gene expression in wild type and nrpd1 endosperm 6 days after pollination - 10 samples. Balanced (Replicate1) GSM2858422 Balanced (Replicate2) GSM2858423 Balanced (Replicate3) GSM2858424 Balanced (Replicate4) GSM2482916 Balanced (Replicate5) GSM2482917
Publication Title
Paternally Acting Canonical RNA-Directed DNA Methylation Pathway Genes Sensitize Arabidopsis Endosperm to Paternal Genome Dosage.
Alternate Accession IDs
Sample Metadata Fields
Subject
View Samples- Caenorhabditis elegans
- 146 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
The principal toxicity of acute organophosphate (OP) pesticides poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethalityparticularly through the inhibition of AChEstudies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms.
Publication Title
Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Abstract
Publication Title
Gene expression profiles in skeletal muscle after gene electrotransfer.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Nonsense-mediated mRNA decay (NMD) is a molecular pathway of mRNA surveillance that ensures rapid degradation of mRNAs containing premature translation termination codons (PTCs) in eukaryotes. Originally, NMD was thought of as a quality control pathway that targets non-functional mRNAs arising from mutations and splicing errors. More recently, NMD has been shown to also regulate normal gene expression and NMD thus emerged as one of the key post-transcriptional mechanisms of gene regulation. We have now systematically analyzed the molecular mechanism of variable NMD efficiency and used different HeLa cell strains as a model system. The results of this analysis show that NMD efficiency can be remarkably variable and represents a stable characteristic of these strains. Low NMD efficiency is shown to be functionally related to the reduced abundance of the exon junction component RNPS1 in one of the HeLa strain analyzed. Furthermore, restoration of functional RNPS1 expression, but not of NMD-inactive mutant proteins, also restores efficient NMD in the RNPS1 deficient cell line. We conclude that cellular concentrations of RNPS1 modify NMD efficiency and propose that the cell type specific co-factor availability represents a novel principle that controls NMD.
Publication Title
The abundance of RNPS1, a protein component of the exon junction complex, can determine the variability in efficiency of the Nonsense Mediated Decay pathway.
Alternate Accession IDs
Sample Metadata Fields
Sex, Disease, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Here we report the discovery of highly potent and selective EZH2 small molecule inhibitors, their validation by a cellular thermal shift assay, their application across a large lymphoma cell panel and their efficacy in GCBDLBCL xenograft models. Overall design: RNA-seq of KARPAS-422 cell line RNA, in duplicate, treated with DMSO as control, and EZH2 inhibitors CPI360, EPZ-6438 and GSK126. Eight samples in total.
Publication Title
EZH2 inhibitor efficacy in non-Hodgkin's lymphoma does not require suppression of H3K27 monomethylation.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To characterize gene response in RPE65-/- mouse model of Lebers congenital amaurosis during progression of the disease, we analyzed differential gene expression in retinae early in the development of the disease, namely before and at the onset of photoreceptor cell death in knock-out mice of 2, 4 and 6 months of age.
Publication Title
Biological characterization of gene response in Rpe65-/- mouse model of Leber's congenital amaurosis during progression of the disease.
Alternate Accession IDs
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The long-term effects of neonatal intermittent hypoxia (IH), an accepted model of apnea-induced hypoxia, are unclear. We have previously shown lasting programming effects on the HPA axis in adult rats exposed to neonatal IH. We hypothesized that neonatal rat exposure to IH will subsequently result in a heightened inflammatory state in the adult. Rat pups were exposed to normoxia (control) or six cycles of 5% IH or 10% IH over one hour daily from postnatal day 2 6. Plasma samples from blood obtained at 114 days of age were analyzed by assessing the capacity to induce transcription in a healthy peripheral blood mononuclear cell (PBMC) population and read using a high-density microarray. The analysis of plasma from adult rats previously exposed to neonatal 5% IH vs. 10% IH resulted in 2,579 significantly regulated genes including increased expression of Cxcl1, Cxcl2, Ccl3, Il1a, and Il1b. We conclude that neonatal exposure to intermittent hypoxia elicits a long-lasting programming effect in the adult resulting in an upregulation of inflammatory-related genes.
Publication Title
Intermittent neonatal hypoxia elicits the upregulation of inflammatory-related genes in adult male rats through long-lasting programming effects.
Alternate Accession IDs
Sample Metadata Fields
Sex
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Drosophila tdf, another name apontic (apt), encodes a bZIP transcription factor that is required for the development of trachea, heart, head and neural system. However, little is known about the target of TDF/Apt.
Publication Title
Evolutionarily conserved transcription factor Apontic controls the G1/S progression by inducing cyclin E during eye development.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
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SRP059448- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Purpose: Examine the effect of the long non-coding RNA PARROT on the transcriptome in HeLa cells. Overall design: Total RNA-seq of RNA from cells treated with the control knock-down (NK) or depleted of ENST00000046668 (PARROT) with two different siRNAs (si1 and si2) for 24h.
Publication Title
The long non-coding RNA PARROT is an upstream regulator of c-Myc and affects proliferation and translation.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
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