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GSE12147
Mus musculus
30 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The nuclear receptor PPARalpha is recognized as the primary target of the fibrate class of hypolipidemic drugs and mediates lipid lowering in part by activating a transcriptional cascade that induces genes involved in the catabolism of lipids. We report here the characterization of three novel PPARalpha agonists with therapeutic potential for treating dyslipidemia. These structurally related compounds display potent and selective binding to human PPARalpha and support robust recruitment of coactivator peptides in vitro. These compounds markedly potentiate chimeric transcription systems in cell-based assays and strikingly lower serum triglycerides in vivo. The transcription networks induced by these selective PPARalpha agonists were assessed by transcriptional profiling of mouse liver after acute and chronic treatment. The induction of several known PPARalpha target genes involved with fatty acid metabolism were observed, reflecting the expected pharmacology associated with PPARalpha activation. We also noted the downregulation of a number of genes related to immune cell function, the acute phase response, and glucose metabolism; suggesting that these compounds may have anti-inflammatory action in the mammalian liver. Taken together, these studies articulate the therapeutic promise of a selective PPARalpha agonist.
Publication Title
Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 21 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Rats were given pulmonary embolism by i.v. injection of 25 micron polystyrene microspheres or 0.01% Tween20 solution as vehicle control
Publication Title
Differential effect of mild and severe pulmonary embolism on the rat lung transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 45 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Time and dose related expression profiles of rat right heart tissue in microsphere bead model for Pulmonary embolism
Publication Title
Transcriptional profile of right ventricular tissue during acute pulmonary embolism in rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Pulmonary vascular occlusions due to thromboemboli can result in pulmonary hypertension and right heart damage. Treatments to clear the vascular obstructions such as i.v. heparain or thrombolytics can resolve the hypertension but right ventricular damage often occurs first. Methods of protecting the right ventricle from hypertensive damage during the course of acute treatment to clear the thromboemboli are needed. Monocyte- and neutrophil-mediated inflammation and fibrosis are associated with chronic right ventricular damage but the pathways involved are not understood. A comprehesive survey of gene expression during chronic pulmonary embolism verses control rats has been conducted in this study.
Publication Title
Transcriptional changes in right ventricular tissues are enriched in the outflow tract compared with the apex during chronic pulmonary embolism in rats.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
There are a few markers available to distinguish hepatic stellate cells (HSCs), portal fibroblasts (PFs), and mesothelial cells (MCs) in the adult mouse liver.
Publication Title
Characterization of hepatic stellate cells, portal fibroblasts, and mesothelial cells in normal and fibrotic livers.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2500
Description
Dazl (deleted in azoospermia like) is a member of the DAZ family of germ cell-restricted RNA binding proteins required for gametogenesis from worm to human. The direct RNA targets and functions of these essential proteins are poorly understood. Here, we generated high-resolution, transcriptome-wide maps of Dazl-RNA interactions in mouse testes. These maps provide important insights into the mechanism of Dazl recruitment to mRNA and reveal Dazl binding to thousands of mRNAs predominantly through sequence-specific interactions near the polyA tail. Using transgenic mice and fluorescence activated cell sorting (FACS), we isolated DAZL knockout germ cells and used RNA-Seq to identify mRNAs sensitive to DAZL-ablation. Intersecting the RNA-Seq and Dazl-RNA interaction datasets revealed that Dazl enhances expression of a subset of directly-bound transcripts, namely mRNAs for a network of essential cell cycle regulatory genes. Collectively, our integrative analysis delineates a Dazl-dependent post-transcriptional gene regulatory program essential for mammalian germ cell maintenance. Overall design: PolyA Seq libraries generated from isolated spermatogonial cells
Publication Title
DAZL Regulates Germ Cell Survival through a Network of PolyA-Proximal mRNA Interactions.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
A persistent and non-resolving inflammatory response to accumulating A peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating A peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many pro-inflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing A-induced inflammation represent a relatively unexplored area.
Publication Title
Suppression of Alzheimer-associated inflammation by microglial prostaglandin-E2 EP4 receptor signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
TCF-1 is an HMG family transcription factor which is known to be critical for T cell development. We discovered that it has a unique role in suppressing malignant transformation of developing thymocytes at early stages. We identified ID2 and LEF-1 as key TCF-1 target genens in tumor suppression.
Publication Title
The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Medulloblastoma (MB) is the most common malignant primary pediatric brain cancer. Among the most aggressive subtypes, Group 3 and Group 4 originate from stem/progenitor cells, frequently metastasize, and often display the worst prognosis, yet, as the names imply, we know the least about the molecular mechanisms driving their progression. Here, we show that the transcription factor orthodenticle homeobox 2 (OTX2) promotes self-renewal while inhibiting differentiation in vitro and increases tumor-initiating capacity from MB stem cell populations in vivo. Characterization of the OTX2 regulatory network revealed a novel relationship between OTX2 and genes associated with multiple axon guidance signaling pathways in Group 3 and Group 4 MB stem/progenitor cells. In particular, OTX2 levels were negatively correlated with semaphorin (SEMA) signaling, as expression of 9 SEMA pathway genes is upregulated following OTX2 knockdown with some being potential direct OTX2 targets. Importantly, this negative correlation between OTX2 and SEMA pathway genes was also observed in patient samples, with lower expression of SEMA4D associated with poor outcome in Group 3 and 4 tumors. Functional studies using established and newly derived MB cell lines demonstrated that increased levels of SEMA pathway genes are associated with decreased self-renewal and growth, and that RHO signaling, known to mediate the effects of SEMA genes, is contributing to the OTX2 KD phenotype. Our study provides critical mechanistic insight into the networks controlled by OTX2 in self-renewing MB cells and reveals novel roles for axon guidance genes and their downstream effectors as putative tumor suppressors and therapeutic targets in Group 3 and Group 4 MB.
Publication Title
Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Sample Metadata Fields
Cell line
View Samples