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GSE40666
Mus musculus
25 Downloadable Samples
Affymetrix Mouse Expression 430A Array (moe430a)
Description
Type 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4- dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 as compared to STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation.
Publication Title
Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glucocorticoids (GC) have a major impact on the biology of normal and malignant cells of the lymphoid lineage. This includes induction of apoptosis which is exploited in the therapy of acute lymphoblastic leukemia (ALL) and related lymphoid malignancies. MicroRNAs (miRNAs) and the related mirtrons are ~22 nucleotide RNA molecules implicated in the control of essential biological functions including proliferation, differentiation and apoptosis. They derive from polymerase-II transcripts but whether GCs regulate miRNA-encoding transcription units is not known. We investigated miRNA/mirtron expression and GC regulation in 8 ALL in vitro models and 13 ALL children undergoing systemic GC monotherapy using a combination of expression profiling techniques, real time RT-PCR and northern blotting to detect mature miRNAs and/or their precursors. We identified a number of GC-regulated miRNAs/mirtrons, including the myeloid-specific miR-223 and the apoptosis and cell cycle arrest-inducing mir15~16 cluster. Thus, the observed complex changes in miRNA/mirtron expression during GC treatment might contribute to the anti-leukemic GC effects in a cell context dependent manner.
Publication Title
Glucocorticoid-regulated microRNAs and mirtrons in acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
IlluminaHiSeq2000
Description
ETS1 and RAS/ERK regulate a common gene expression program in establishing enviroment suitable for prostate cancer cell migration. Overall design: mRNA profiles of luciferase knockdown (WT), ETS1 knockdown, and U0126 treated DU145 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.
Publication Title
Interaction with ZMYND11 mediates opposing roles of Ras-responsive transcription factors ETS1 and ETS2.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarrays to detail the global programme of gene expression underlying palate development by persistent expression in R26Pax3 mice and identified distinct classes of up-regulated and down-regulated genes during this process.
Publication Title
Persistent expression of Pax3 in the neural crest causes cleft palate and defective osteogenesis in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established.
Publication Title
Assessing individual differences in genome-wide gene expression in human whole blood: reliability over four hours and stability over 10 months.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- IlluminaHiSeq2000
Description
Knockdowns of c-JUN and JUND had opposite effects on PC3 prostate cell migration. We predicted that c-JUN and JUND control the same set of cell migration genes, but in opposite directions. To test this hypothesis, mRNA with expression changes in c-JUN and JUND knockdown PC3 cell lines were compared to mRNA levels in control (luciferase knockdown) PC3 cells by RNA-seq. Overall design: mRNA profiles of luciferase knockdown (WT), c-Jun knockdown, and Jun-D knockdown in PC3 cells were generated using deep sequencing, in triplicate, using Illumina HiSeq. Knockdowns were stable shRNA expression from a lentiviral construct selected with puromycin.
Publication Title
Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression.
Publication Title
Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 9 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The mineralocorticoid aldosterone mainly produced by the adrenal gland is essential for life but an abnormal excessive secretion causes severe pathological effects including hypertension and target organ injury in the heart and kidney. The aim of this study was to determine the gene regulatory network triggered by aldosterone secretagogues in a non transformed cell system. Freshly isolated rat adrenal zona glomerulosa cells were stimulated with the two main aldosterone secretagogues, angiotensin II and potassium, for two hours and subjected to whole genome expression studies using multiple biological and bioinformatics tools. Several genes were differentially expressed by Ang II (n=133) or potassium (n=216). Genes belonging to the nucleic acid binding and transcription factor activity categories were significantly enriched. A subset of the most regulated genes were confirmed by real-time RT-PCR and then their expression analyzed in time curve studies. Differentially expressed genes were grouped according to their time-response expression pattern and their promoter regions analyzed for common regulatory transcription factors binding sites. Finally, data mining with gene promoters, transcription factors and literature databases were performed to generate gene interaction networks for either Ang II or potassium. This study provides for the first time a complete study of the genes that are regulated, and the interaction between them, by aldosterone secretagogues in rat adrenal cells. Increasing our knowledge of adrenal physiology and gene regulation in non transformed cell systems would lead us to a better approach for discovery of candidate genes involved pathological conditions of the adrenal cortex.
Publication Title
Gene expression profile in rat adrenal zona glomerulosa cells stimulated with aldosterone secretagogues.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 71 Downloadable Samples
- Illumina HiSeq 4000
Description
In response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. We determined that activation of the Eif2ak2-Eif2a axis is the key mediator of translation initiation block in late phase sepsis. Reversal of this axis mitigated kidney injury. Furthermore, temporal profiling of the kidney translatome revealed that multiple genes involved in formation of the initiation complex were translationally altered during bacterial sepsis. Collectively, our findings implicate that translation shutdown is indifferent to the specific initiating pathogen and is an important determinant of tissue injury in sepsis. Overall design: Bulk 20 um thickness specimens from cross-sectional human kidney biopsies embedded in OCT underwent RNA sequencing. All subjects had ATN, AIN, or a mix of both conditions.
Publication Title
Bacterial sepsis triggers an antiviral response that causes translation shutdown.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We used RNA sequencing to characterize gene expression of CD4+ CD8a+ double positive (DP), Foxp3+ Treg (TR) and CD4+ single positive (SP) cells in the lamina propria (LP) and intraepithelial compartment (IEL) that had differentiante from the same clonal transnuclear (TN) precursor. Overall design: We adoptively transferred CD4+ CD8a- Foxp3-GFP- isolated from pTregTN/RKO/Foxp3-GFP mice into TCRaßKO hosts. After 6 weeks, we sorted transferred CD4+ CD8a+, Foxp3+ pTreg as well as unconverted CD4+ CD8a- Foxp3-GFP- from the small intestine LP and IEL compartments for whole transcriptome analysis by mRNA sequencing.
Publication Title
Tissue-specific emergence of regulatory and intraepithelial T cells from a clonal T cell precursor.
Sample Metadata Fields
Specimen part, Subject
View Samples