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.
The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy.
Specimen part
View SamplesRats were given pulmonary embolism by i.v. injection of 25 micron polystyrene microspheres or 0.01% Tween20 solution as vehicle control
Differential effect of mild and severe pulmonary embolism on the rat lung transcriptome.
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View SamplesWe constructed a primary lung cell model to permit regulated expression of KRASG12D. To do this, we leveraged a non-transformed, immortalized, human primary bronchial epithelial cell line (HBEC; hTert, CDK4, TP53 knockdown) that remains anchorage dependent and do not develop tumors when implanted into mice. We next modified these cells by stably integrating a regulatable KRASG12D allele, iKRASG12D, such that physiological expression of mutant KRAS is activated upon addition of doxycycline. The HBEC-iKRAS (WT) cell line and HBEC-iKRASG12D (MUT) cell line were propagated with or without Doxycycline (500ng/ml) respectively. RNA profiling of HBEC-iKRASG12D and HBEC-iKRASWT cells revealed widespread changes for HBECs harboring the activated KRAS allele in the presence of Dox. Within the KRASG12D-induced genes, the Molecular Signatures Database identified the oncogenic RAS signature as a top-enriched gene set. Upregulation of Ras signaling in Dox-treated HBEC-iKRASG12D cells was also supported by a significant overlap with a KRAS signature previously characterized by Singh et al.
In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer.
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View SamplesTime and dose related expression profiles of rat right heart tissue in microsphere bead model for Pulmonary embolism
Transcriptional profile of right ventricular tissue during acute pulmonary embolism in rats.
No sample metadata fields
View SamplesPulmonary 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.
Transcriptional changes in right ventricular tissues are enriched in the outflow tract compared with the apex during chronic pulmonary embolism in rats.
Sex
View SamplesDazl (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
DAZL Regulates Germ Cell Survival through a Network of PolyA-Proximal mRNA Interactions.
Sex, Specimen part, Cell line, Subject
View SamplesThere are a few markers available to distinguish hepatic stellate cells (HSCs), portal fibroblasts (PFs), and mesothelial cells (MCs) in the adult mouse liver.
Characterization of hepatic stellate cells, portal fibroblasts, and mesothelial cells in normal and fibrotic livers.
Specimen part
View SamplesA 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.
Suppression of Alzheimer-associated inflammation by microglial prostaglandin-E2 EP4 receptor signaling.
Specimen part
View SamplesThe 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.
Molecular characterization of novel and selective peroxisome proliferator-activated receptor alpha agonists with robust hypolipidemic activity in vivo.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterization of a novel OTX2-driven stem cell program in Group 3 and Group 4 medulloblastoma.
Cell line
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