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Rattus norvegicus
6 Downloadable Samples
Illumina HiSeq 2500
Description
SOX9 is a transcriptional activator required for chondrogenesis, and SOX5 and SOX6 are closely related DNA-binding proteins that critically enhance its function. We used RNA-seq to charatierize a rat chondrosarcoma (RCS) cells as a faithful model for proliferating/early prehypertrophic growth plate chondrocytes and ChIP-seq to gain novel insights into the full spectrum of the target genes and modes of action of this chondrogenic trio. Overall design: RNAs were isolated from three bioogical replicatse of rat chondrosarcoma (RCS) cells and rib samples for RNA-seq experiments.
Publication Title
The transcription factors SOX9 and SOX5/SOX6 cooperate genome-wide through super-enhancers to drive chondrogenesis.
Sample Metadata Fields
No sample metadata fields
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GSE5587- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Early Growth Response (Egr) family of transcription factors consists of 4 members (Egr1-4) that are expressed in a wide variety of cell types. A large body of evidence point to a role for Egr transcription factors in growth, survival, and differentiation. A major unanswered question is whether Egr transcription factors serve similar functions in diverse cell types by activating a common set of target genes. Signal transduction cascades in neurons and lymphocytes show striking parallels. Activation of either cell type activates the Ras-MAPK pathway and, in parallel, leads to increases in intracellular calcium stimulating the calcineurin-NFAT pathway. In both cell types, the strength of the activation signal affects the cellular outcomes and very strong stimuli lead to cell death. Notably both these pathways converge on the induction of Egr genes. We believe that downstream targets of Egr transcription factors in lymphocytes may also be activated by Egr factors in activated neurons. There is precedence for common target gene activation in these two cell types: apoptosis in both activated T cells and methamphetamine stimulated neurons occurs via FasL induction by NFAT transcription factors. We propose to use developing T lymphocytes (thymocytes) as a model system for discovery of Egr-dependent target genes for several reasons. First, we have observed a prominent survival defect in thymocytes from mice deficient in both Egr1 and Egr3 (1/3 DKO) and a partial differention block in the immature double negative (DN) stage. In addition, thymocytes are an easily manipulatable cell type, and the DN subpopulation affected in 1/3 DKO mice can be isolated to very high purity. We anticipate that 1/3 DKO thymocytes will provide an excellent experimental system that will provide insight into Egr-dependent transcription in neuronal development, activation, and death.
Publication Title
Redundant role for early growth response transcriptional regulators in thymocyte differentiation and survival.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 9 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Domoic acid (DA) is a neuroexcitatory amino acid that is naturally produced by some marine diatom species of the genus Pseudo-nitzschia. Ingestion of DA-contaminated seafood by humans results in a severe neurotoxic disease known as amnesic shellfish poisoning (ASP). Clinical signs of ASP include seizures and neuronal damage from activation of AMPA and kainate receptors. However, the impacts of DA exposure at levels below those known to induce outward signs of neurobehavioral exicitotoxicity have not been well characterized. To further understand the mechanisms of neurotoxic injury associated with DA exposure, we examined the transcriptome of whole brains from zebrafish (Danio rerio) receiving intracoelomic (IC) DA at both symptomatic and asymptomatic doses. A majority of zebrafish exposed to high-dose DA (1.2 g DA/g) exhibited clinical signs of neuroexcitotoxicity (EC50 of 0.86 g DA/g) within 5 to 20 minutes of IC injection. All zebrafish receiving low-dose DA (0.47 g DA/g) or vehicle only maintained normal behavior. Microarray analysis of symptomatic and asymptomatic exposures collectively yielded 306 differentially expressed genes (1.5-fold, p = 0.05) predominately represented by signal transduction, ion transport, and transcription factor functional categories. Transcriptional profiles were suggestive of neuronal apoptosis following an overwhelming of protective adaptive pathways. Further, potential molecular biomarkers of neuropathic injury, including Nrdg4, were identified and may be relevant to DA exposure levels below that causing neurobehavioral injury. Our results validate zebrafish as a vertebrate model to study mechanisms of DA neurotoxicity and provide a basis for identifying pathways of DA-induced injury as well as biomarkers of asymptomatic and symptomatic DA exposure levels.
Publication Title
Gene expression profiles in zebrafish brain after acute exposure to domoic acid at symptomatic and asymptomatic doses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
We performed RNA-seq and ChIP-seq on clones of human cell lines carrying an inducible XIST transgene on 1p, 8p, or 12q to study the effects of allelic silencing in cis Overall design: Total gene expression and allelic changes were examined in HT1080 clones carrying an inducible XIST transgene on 1p, 8p, or 12q after induction by doxycycline. A replicate was done for the 8p clone treated with DOX. An additional 1p clone integrated with an empty vector, and an 1p, 8p, and 12q clone without induction were included as controls. ChIP was performed on the 8p clone to investigate the changes in H3K27 acetylation and trimethylation.
Publication Title
Impact of flanking chromosomal sequences on localization and silencing by the human non-coding RNA XIST.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. Some rare severe clinical cases have however been reported without investigation of host immune responses or viral virulence. In this present study, we investigate, for the first time, phenotypic and functional features together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty PHIP were enrolled as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had a huge lymphocytosis marked by massive expansion of NK and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C+ NK cells, CD16+ V2- T cells and conventional HCMV-specific CD8+ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both huge lymphocytosis and excessive lymphocyte activation could contribute to a massive cytokine production known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV-infection in immunocompetent individuals.
Publication Title
Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Post-translational regulation of the MYC Transcription Factor (TF), including its phosphorylation and ubiquitination, plays an important role in determining cell proliferation and apoptosis and has been implicated in tumorigenesis. Using a computational systems biology approach, followed by biochemical and functional validation, we have characterized the role of the STK38 kinase, an NDR family serine-threonine kinase, as a key modulator of MYC transcriptional activity in human B cells, affecting MYC protein stability in a signal-dependent fashion. Specifically, we show that in human B lymphoma ST486 cells STK38 is a key mediator of BCR pathway signaling, affecting MYC protein turnover and its phosphorylation at Ser62 in kinase-activity-dependent manner. STK38 inactivation abrogates apoptosis following BCR activation while its silencing mediates MYC protein degradation via canonical proteolytic pathways. This suggests that STK38 could provide an effective therapeutic target in MYC-dependent malignancies.
Publication Title
STK38 is a critical upstream regulator of MYC's oncogenic activity in human B-cell lymphoma.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 21 Downloadable Samples
Description
Critical roles for DNA methylation in embryonic development are well established, but less is known about the roles of DNA methylation during trophoblast development, the extraembryonic lineage that gives rise to the placenta. Here we dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b-null trophoblast. We find that most gene deregulation is explained by an erasure of maternal methylation in the oocyte, but partially independent of loss of imprinting of the trophoblast-essential Ascl2 gene. Our results reveal that maternal DNA methylation controls multiple differentiation and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms. Overall design: mRNA-seq and WGBS-seq of maternal Dnmt3a/3b-null trophoblast; mRNA-seq of maternal Ascl2 KO trophoblast
Publication Title
Maternal DNA Methylation Regulates Early Trophoblast Development.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 384 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of the transcriptome of mouse models of prostate cancer to assemble a mouse prostate cancer interactome.
Publication Title
Cross-species regulatory network analysis identifies a synergistic interaction between FOXM1 and CENPF that drives prostate cancer malignancy.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of the transcriptome of mouse models of prostate cancer. NP (Nkx3.1CreERT2/+; Ptenfloxed/floxed) mice develop non-metastatic tumors while NPK (Nkx3.1CreERT2/+; Ptenfloxed/floxed; KrasG12D/+) mice develop metastatic tumors
Publication Title
ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Mus musculus
- 31 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples