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GSE5424
Mus musculus
8 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Background: The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. Despite its important role during development, there are still relatively few genes with specific expression in the organizer and its derivatives. Foxa2 is a forkhead transcription factor that is absolutely required for formation of the mammalian equivalent of the organizer, the node, the axial mesoderm and the definitive endoderm (DE). However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined.
Publication Title
Microarray analysis of Foxa2 mutant mouse embryos reveals novel gene expression and inductive roles for the gastrula organizer and its derivatives.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
IRAK-4 is an essential component of the signal transduction complex downstream of the IL-1- and Toll-like receptors. Though regarded as the first kinase in the signaling cascade, the role of IRAK-4 kinase activity versus its scaffold function is still controversial. In order to investigate the role of IRAK-4 kinase function in vivo, knock-in mice were generated by replacing the wild type IRAK-4 gene with a mutant gene encoding kinase deficient IRAK-4 protein (IRAK-4 KD). Analysis of embryonic fibroblasts and macrophages obtained from IRAK-4 KD mice with a number of experimental techniques demonstrated that they greatly lack responsiveness to stimulation with IL-1b or a Toll-like receptor 7 (TLR7) agonist. One of the techniques used, microarray analysis, identified IRAK-4 kinase-dependent IL-1b response genes in mouse embryonic fibroblasts and revealed that the induction of IL-1b-responsive mRNAs was largely ablated in IRAK-4 KD cells. In summary, our results suggest that IRAK-4 kinase activity plays a critical role in IL-1R/TLR7-mediated induction of inflammatory responses.
Publication Title
IRAK-4 kinase activity is required for interleukin-1 (IL-1) receptor- and toll-like receptor 7-mediated signaling and gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regeneration of skeletal muscle is dependent on the function of tissue-resident muscle stem cells (MuSC), known as satellite cells. MuSC dysfunction is central to muscle pathophysiology, including in age-associated loss of muscle regenerative capacity and congenital disorders such as Duchenne muscular dystrophy. Despite the central role of satellite cells in muscle regeneration, the signals controlling the balance between muscle stem cell quiescence, proliferation, and differentiation remain incompletely understood. Knowledge of the signals that maintain a quiescent state is particularly lacking, yet such cues are crucial to maintaining a stem cell reservoir that can meet the needs of regeneration throughout life. Here we identify Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent and essential trans-acting regulator of satellite cell quiescence. Key to this discovery is the development of a novel in vivo imaging-based screening strategy allowing identification of proteins that do not induce in vitro proliferation, but instead maintain MuSCs in a non-mitotic state, poised for rapid robust expansion upon transplantation. We demonstrate that OSM induces reversible exit from the cell cycle and induction of a global transcriptional program significantly enriched within a newly established satellite cell quiescence signature. Genetic ablation of the OSM receptor in mice demonstrates that signaling via OSM/R is essential for maintenance of satellite cell quiescence, and for proper skeletal muscle regeneration in vivo. Given that aberrant activation and exhaustion of stem cells is seen in a variety of disorders, OSM constitutes an attractive therapeutic target in muscle disease states.
Publication Title
Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Rod-derived Cone Viability Factor (RdCVF, alias nxnl1) is a retina-specific protein identified for its therapeutic potential in supporting cone survival during retinal degeneration.
Publication Title
The disruption of the rod-derived cone viability gene leads to photoreceptor dysfunction and susceptibility to oxidative stress.
Sample Metadata Fields
Disease, Disease stage
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A nxnl2 knockout mouse model was created and the transcriptome used to demonstrate that the retina is compromised by the absence of nxnl2.
Publication Title
Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The transcriptional programme controlled by Runx1 during early embryonic blood development.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcription factors have long been recognised as powerful regulators of mammalian development, yet it is largely unknown how individual key regulators operate within wider regulatory networks. Here we have used a combination of global gene expression and chromatin-immunoprecipitation approaches across four ES-cell-derived populations of increasing haematopoietic potential to define the transcriptional programme controlled by Runx1, an essential regulator of blood cell specification. Integrated analysis of these complementary genome-wide datasets allowed us to construct a global regulatory network model, which suggested that core regulatory circuits are activated sequentially during blood specification, but will ultimately collaborate to control many haematopoietically expressed genes. Using the CD41/integrin alpha 2b gene as a model, cellular and in vivo studies showed that CD41 is controlled by both early and late circuits in fully specified blood cells, but initiation of CD41 expression critically depends on a later subcircuit driven by Runx1. Taken together, this study represents the first global analysis of the transcriptional programme controlled by any key haematopoietic regulator during the process of early blood cell specification. Moreover, the concept of interplay between sequentially deployed core regulatory circuits is likely to represent a design principle widely applicable to the transcriptional control of mammalian development.
Publication Title
The transcriptional programme controlled by Runx1 during early embryonic blood development.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The adenosine 2A receptor (A2AR) is expressed on regulatory T cells (Tregs), but the functional significance is currently unknown. We compared the gene expression between wild-type (WT) and A2AR knockout (KO) Tregs and between WT Tregs treated with vehicle or a selective A2AR agonist.
Publication Title
Autocrine adenosine signaling promotes regulatory T cell-mediated renal protection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The loss of REST in uterine fibroids promotes aberrant gene expression and enables mTOR pathway activation
Publication Title
Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Understanding the molecular underpinnings of cancer is of critical importance to developing targeted intervention strategies. Identification of such targets, however, is notoriously difficult and unpredictable. Malignant cell transformation requires the cooperation of a few oncogenic mutations that cause substantial reorganization of many cell features and induce complex changes in gene expression patterns. Genes critical to this multi-faceted cellular phenotype thus only have been identified following signaling pathway analysis or on an ad hoc basis. Our observations that cell transformation by cooperating oncogenic lesions depends on synergistic modulation of downstream signaling circuitry suggest that malignant transformation is a highly cooperative process, involving synergy at multiple levels of regulation, including gene expression. Here we show that a large proportion of genes controlled synergistically by loss-of-function p53 and Ras activation are critical to the malignant state. Remarkably, 14 among 24 such 'cooperation response genes' (CRGs) were found to contribute to tumor formation in gene perturbation experiments. In contrast, only one in 14 perturbations of genes responding in a non-synergistic manner had a similar effect. Synergistic control of gene expression by oncogenic mutations thus emerges as an underlying key to malignancy and provides an attractive rationale for identifying intervention targets in gene networks downstream of oncogenic gain and loss-of-function mutations.
Publication Title
Synergistic response to oncogenic mutations defines gene class critical to cancer phenotype.
Sample Metadata Fields
No sample metadata fields
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