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GSE45234
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Oxidative stress is a hallmark of inflammation in infection or sterile tissue injury. We show that partially oxidized phospholipids of microvesicles (MVs) from plasma of patients with rheumatoid arthritis or cells exposed to oxidative stress induce activation of TLR4. MVs from healthy donors or reconstituted synthetic MVs can be converted to TLR4 agonists by limited oxidation, while prolonged oxidation abrogates the activity. Activation by MVs mimics the mechanism of TLR4 activation by LPS. However, LPS and MVs induce significantly different transcriptional response profile in mouse BMDMs with a strong inflammation-resolving component induced by the endogenous signals. MVs thus represent a ubiquitous endogenous danger signal released under the oxidative stress, which underlies the pervasive role of TLR4 signaling in inflammation.
Publication Title
Toll-like receptor 4 senses oxidative stress mediated by the oxidation of phospholipids in extracellular vesicles.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared whole genome expression profiles of GSCs with normal human cortex, human neural stem cells (hNSC) from fetal cortex, glioblastoma (GBM) primary, and recurrent tumors to find GSC-specific plasma membrane transcripts.
Publication Title
Myelin-forming cell-specific cadherin-19 is a marker for minimally infiltrative glioblastoma stem-like cells.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Angiogenesis in cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture.
Publication Title
Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Angiogenesis in collagen gel cultures of rat aorta begins with neovessels sprouting from the aortic explant within the first three days of culture.
Publication Title
Macrophage-derived tumor necrosis factor-alpha is an early component of the molecular cascade leading to angiogenesis in response to aortic injury.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 4 Downloadable Samples
NextSeq 500
Description
A complex network of inflammation succeeds somatic cell transformation and malignant disease. Immune cells and their associated molecules are responsible for detecting and eliminating cancer cells as they establish themselves as the precursors of a tumour. By the time a patient has a detectable solid tumour, cancer cells have escaped the initial immune response mechanisms. To date, no model exists to allow us to study the underlying mechanisms that govern the initial phase of the immune response as cells are transformed to become the precursors of cancer. Here we describe the development of an innovative double binary animal model designed in zebrafish for exploring regulatory programming of the myeloid cells as they respond to oncogenic transformed melanocytes. This modular system harnesses the power of zebrafish genetics. For studies of melanocyte transformation we generated a hormone-inducible binary system allowing for temporal control of different Ras-oncogene (NRasK61Q, HRasG12V, KRasG12V) expression in melanocytes allowing us to truly study melanoma initiation. This binary model was then coupled to a model for regulatory profiling of the active transcriptome of macrophages and neutrophils which is based on the in vivo biotinylation of nuclei and their subsequent isolation by streptavidin affinity purification. For the first time regulatory profiling of neutrophils as they respond to the earliest precursors of melanoma, revealed a number of factors upregulated in neutrophils that may promote progression to melanoma including fgf1, fgf6, cathepsin H, cathepsin L, galectin 1 and galectin 3. Overall design: We report the design of a double binary approach in zebrafish to study the neutrophil response to transformed melanocytes. By coupling a novel inducible model for melanocyte transformation to a model for the in vivo biotinylation of neutrophil nuclei we can isolate the neutrophil nuclei directly from the in vivo context allowing for RNA-seq analysis of the active transcriptome.
Publication Title
Generation of a double binary transgenic zebrafish model to study myeloid gene regulation in response to oncogene activation in melanocytes.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The goal was to find pathways which were enriched in the resistant group of cells. Overall design: mRNA profiles of both cell lines were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Publication Title
IGF1R upregulation confers resistance to isoform-specific inhibitors of PI3K in PIK3CA-driven ovarian cancer.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Xenopus laevis
- 31 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
A conserved molecular pathway has emerged controlling endoderm formation in Xenopus zebrafish and mice. Key genes in this pathway include Nodal ligands and transcription factors of the Mix-like paired homeodomain class, Gata4-6 zinc finger factors and Sox17 HMG domain proteins. While a linear epistatic pathway has been proposed, the precise hierarchical relationships between these factors and their downstream targets are largely unresolved. Here we used a combination of microarray analysis and loss-of-function experiments to examine the global regulatory network controlling Xenopus endoderm formation. We identified over 300 transcripts enriched in the gastrula endoderm, including most of the known endoderm regulators as well as over a hundred uncharacterized genes. Surprisingly only 10% of the endoderm transcriptome is regulated as predicted by the current linear model. We find that Nodals, Mixer and Sox17 have both shared and distinct sets of downstream targets and that a number of unexpected autoregulatory loops exist between Sox17 and Gata4-6, Sox17 and Bix1, 2, 4 and between Sox17 and Xnr4. We find that Mixer does not function primarily via Sox17 as previously proposed. This data provides a new insight into the complexity of endoderm formation and will serve as valuable resource for establishing a complete endoderm gene regulatory network.
Publication Title
Global analysis of the transcriptional network controlling Xenopus endoderm formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The following abstract from the submitted manuscript describes the major findings of this work.
Publication Title
A role for peroxisome proliferator-activated receptor γ coactivator-1 in the control of mitochondrial dynamics during postnatal cardiac growth.
Sample Metadata Fields
Specimen part
View Samples- Xenopus laevis
- 8 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Foregut organogenesis is regulated by inductive interactions between the endoderm and the adjacent mesoderm. We identified genes induced in the foregut progenitors by the adjacent mesoderm.
Publication Title
Sizzled-tolloid interactions maintain foregut progenitors by regulating fibronectin-dependent BMP signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The Cytoplasmic Polyadenylation Element Binding (CPEB)-family of RNA-binding proteins regulates pre-mRNA processing and translation of CPE-containing mRNAs in early embryonic development and synaptic activity. However, the specific functions of each CPEB in the adult organism are poorly understood. Here we show that CPEB4 is required to suppress high fat diet- and aging-induced endoplasmic reticulum (ER) stress, and its subsequent hepatic steatosis. Stress-activated expression of CPEB4 in the liver is controlled through a double layer of regulation. First, Cpeb4 is transcriptionally regulated by the circadian clock and then, its mRNA translation is regulated by the Unfolded Protein Response (UPR) through the upstream Open Reading Frames (uORFs) present in its 5’ UTR. Thus, CPEB4 is synthesized only upon ER-stress but the amplitude of the induction is circadian. In turn, CPEB4 activates a second wave of UPR-translation required to maintain ER and mitochondrial homeostasis. Our results suggest that combined transcriptional and translational regulation of CPEB4 generates a “circadian mediator”, which?coordinates the hepatic UPR activity with periods of high ER protein-folding demand preventing non-alcoholic fatty liver disease (NAFLD). Overall design: mRNA profiles of total liver RNA and liver ER-associated RNA from WT and CPEB4-KO mice
Publication Title
Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress.
Sample Metadata Fields
Subject
View Samples