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GSE29145
Mus musculus
1 Downloadable Sample
Description
Background: Gq-coupled G protein-coupled receptors (GPCR) mediate the actions of a variety of messengers that are key regulators of cardiovascular function. Enhanced Gaq-mediated signaling plays an important role in cardiac hypertrophy and in the transition to heart failure. We have recently described that Gaq acts as an adaptor protein that facilitates PKCz-mediated activation of ERK5 in epithelial cells. Since the ERK5 cascade is known to be involved in cardiac hypertrophy, we have investigated the potential relevance of this pathway in Gq-dependent signaling in cardiac cells.
Publication Title
Protein kinase C (PKC)ζ-mediated Gαq stimulation of ERK5 protein pathway in cardiomyocytes and cardiac fibroblasts.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Description
A permantly active form of the oncogene Akt was expressed in the keratinocytes of the basal proliferative layer of the epidermis. Stem cells of the hair follicle expressing the cell surface marker CD34 were isolated. RNA form the CD34(+) and CD34(-) keratinocytes was extracted and and hybridized to Mouse Genome 430 2.0 Affymetrix arrays.
Publication Title
Akt signaling leads to stem cell activation and promotes tumor development in epidermis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
Description
The epidermal specific ablation of Trp53 gene leads to the spontaneous development of aggressive tumors in mice through a process that is accelerated by the simultaneous ablation of Rb gene. Since alterations of p53-dependent pathway are common hallmarks of aggressive, poor prognostic human cancers, these mouse models can recapitulate the molecular features of some of these human malignancies. To evaluate this possibility, gene expression microarray analysis was performed in mouse samples. The mouse tumors display increased expression of cell cycle and chromosomal instability associated genes. Remarkably, they are also enriched in human embryonic stem cell gene signatures, a characteristic feature of human aggressive tumors. Using cross-species comparison and meta-analytical approaches, we also observed that spontaneous mouse tumors display robust similarities with gene expression profiles of human tumors bearing mutated TP53, or displaying poor prognostic outcome, from multiple body tissues. We have obtained a 20-gene signature whose genes are overexpressed in mouse tumors and can identify human tumors with poor outcome from breast cancer, astrocytoma and multiple myeloma. This signature was consistently overexpressed in additional mouse tumors using microarray analysis. Two of the genes of this signature, AURKA and UBE2C, were validated in human breast and cervical cancer as potential biomarkers of malignancy. Our analyses demonstrate that these mouse models are promising preclinical tools aimed to search for malignancy biomarkers and to test targeted therapies of prospective use in human aggressive tumors and/or with p53 mutation or inactivation.
Publication Title
Gene expression profiling of mouse p53-deficient epidermal carcinoma defines molecular determinants of human cancer malignancy.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 29 Downloadable Samples
Description
Polymorphisms in the interleukin-4 receptor chain (IL-4R) have been linked to asthma incidence and severity, but a causal relationship has remained uncertain. In particular, a glutamine to arginine substitution at position 576 (Q576R) of IL-4R has been associated with severe asthma, especially in African Americans. We show that mice carrying the Q576R polymorphism exhibited intense allergen-induced airway inflammation and remodeling. The Q576R polymorphism did not affect proximal signal transducer and activator of transcription (STAT) 6 activation, but synergized with STAT6 in a gene target and tissue-specific manner to mediate heightened expression of a subset of IL-4 and IL-13responsive genes involved in allergic inflammation. Our findings indicate that the Q576R polymorphism directly promotes asthma in carrier populations by selectively augmenting IL-4Rdependent signaling.
Publication Title
Pathogenicity of a disease-associated human IL-4 receptor allele in experimental asthma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Posterior embryonic axis develops from neuromesodermal progenitors which differentiate into neural tube and paraxial mesoderm
Publication Title
Recapitulating early development of mouse musculoskeletal precursors of the paraxial mesoderm <i>in vitro</i>.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Barrier integrity is central to the maintenance of a healthy immunological homeostasis. Impaired skin barrier function is linked with enhanced allergen sensitization and the development of diseases such as atopic dermatitis (AD), which can precede the development of other allergic diseases such as food allergies and asthma. Epidemiological evidence indicates that children suffering from allergies have lower levels of dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model of AD, we report that a fermentable fibre-rich diet alleviates AD severity and systemic allergen sensitization. The gut-skin axis underpins this phenomenon through SCFA, which strengthen skin barrier integrity by altering mitochondrial metabolism of epidermal keratinocytes. SCFA promote keratinocyte differentiation and the production of key structural lipids, resulting in enhanced barrier function. Our results demonstrate that dietary fibre and SCFA mitigate AD by improving barrier integrity, ultimately limiting early systemic allergen sensitization and development of disease. Overall design: 16 Samples, 4 groups in duplicate
Publication Title
Gut-derived short-chain fatty acids modulate skin barrier integrity by promoting keratinocyte metabolism and differentiation.
Sample Metadata Fields
Genotype, Disease, Disease stage, Treatment, Subject
View Samples- Mus musculus, Homo sapiens
- 10 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Sympathetic neurons of SCG (Superior Cervical Ganglia) send axonal projections either along the external carotid arteries to innervate the salivary glands, or along the internal carotid arteries to the lacrimal and pineal glands, the eye, blood vessels and skin of the head, and the mucosa of the oral and nasal cavities. Previous studies using Wnt1Cre and R26R have defined the neural crest and mesodermal origins of vascular smooth muscle in the heart outflow tract and great vessels, although not specifically of the segments that are relevant for the projections of the SCG neurons. The third pharyngeal arch arteries are lined by neural crest-derived smooth muscle, and consequently, their derivatives, including the entirety of the external carotid arteries and only the base of the internal carotid arteries, also have a neural crest origin. In contrast, the dorsal aortae are lined by smooth muscle that is mesodermal in origin, and as a result, the internal carotid arteries from just above their origination from the common carotid arteries have a mesoderm-derived smooth muscle layer. To address the possibility that guidance cues for SCG neurons are selectively expressed by the external carotid vs. the internal carotid arteries, we isolated these segments of the vasculature from mouse embryos at E13.5 and extracted RNA to screen microarrays for differentially expressed genes.
Publication Title
Endothelins are vascular-derived axonal guidance cues for developing sympathetic neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
Description
Homologue of Enhancer-of-split 1 (Hes1) is a transcription factor that regulates neuronal plasticity, promoting the growth of dendrites and increasing the GABAergic input. A higher expression of Hes1 also results in neuronal resistance against the noxious activity of amyloid beta, the main agent in the advent and progression of the Alzheimer's disease. As a transcription factor, Hes1 controls de expression of many genes. Using the microarray technology we have detected that the expression of one secreted synaptic protein, cerebellin 4 (Cbln4) was particularly increased upon overexpression of Hes1. We also present evidence that Cbln4 plays an essential role in the formation and maintenance of inhibitory GABAergic connections and that either overexpression of Cbln4 in cultured hippocampal neurons or the application of recombinant Cbln4 to the cultures increased the number of GABAergic varicosities and rescued neurons from amyloid beta induced cell death.
Publication Title
Cerebellin 4, a synaptic protein, enhances inhibitory activity and resistance of neurons to amyloid-β toxicity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 1 Downloadable Sample
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC).
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples