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GSE35332
Mus musculus
12 Downloadable Samples
Description
Mast cells, activated by antigen via the high affinity receptor for IgE (FcRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders.
Publication Title
Stem cell factor programs the mast cell activation phenotype.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Interleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its acute effects on mouse mast cells (MCs), IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of chronic IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. We now find that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to antigen. This reduction required >72 h exposure to IL-33 for onset and 1-2 wk for reversion following IL-33 removal. This hypo-responsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation including antigen-mediated calcium mobilization and cytoskeletal reorganization; potentially as a consequence of down-regulation of the expression of PLCg1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to down-regulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease.
Publication Title
IL-33 induces a hyporesponsive phenotype in human and mouse mast cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Description
Transcriptom analysis of stellate sympathetic ganglia after 8 weeks of cardiac pressure overload caused by transverse aortic constriction.
Publication Title
Sympathetic alpha(2)-adrenoceptors prevent cardiac hypertrophy and fibrosis in mice at baseline but not after chronic pressure overload.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Inhibition of miR-33 results in increased cholesterol efflux and HDL-cholesterol levels in mice. In this study we examined the effect of miR-33 inhibition in a mouse model of atherosclerosis and observed significant reduction in atherosclerotic plaque size. At the end of the study, gene expression in macrophages from the atherosclerotic plaques was assessed.
Publication Title
Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 64 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Restricted feeding impacts the hepatic circadian clock of WT mice. Cry1, Cry2 double KO mice lack a circadian clock and are thus expected to show rhythmical gene expression in the liver. Imposing a temporally restricted feeding schedule on these mice shows how the hepatic circadian clock and rhythmic food intake regulate rhythmic transcription in parallel
Publication Title
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Temporally restricted feeding is known to impact the circadian clock. This dataset shows the effects of temporally restricted feeding on the hepatic transcriptome.
Publication Title
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
Description
Temporally restricted feeding has a profound effect on the circadian clock. Fasting and feeding paradigms are known to influence hepatic transcription. This dataset shows the dynamic effects of refeeding mice after a 24hour fasting period.
Publication Title
Time of feeding and the intrinsic circadian clock drive rhythms in hepatic gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
Description
The study analyzes analyzes gene expression changes in the ankle joint in mouse TNFa overexpression models with or without sphingosine kinase 1 activity.
Publication Title
Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 22 Downloadable Samples
Description
Genomic technologies have unmasked molecularly distinct subgroups among tumors of the same histological type; but understanding the biologic basis of these subgroups has proved difficult since their defining alterations are often numerous, and the cellular origins of most cancers remain unknown. We sought to decipher complex genomic data sets by matching the genetic alterations contained within these, with candidate cells of origin, to generate accurate disease models. Using an integrated genomic analysis we first identified subgroups of human ependymoma: a form of neural tumor that arises throughout the central nervous system (CNS). Validated alterations included amplifications and homozygous deletions of genes not yet implicated in ependymoma. Matching the transcriptomes of human ependymoma subgroups to those of distinct types of mouse radial glia (RG)neural stem cells (NSCs) that we identified previously to be a candidate cell of origin of ependymoma - allowed us to select RG types most likely to represent cells of origin of disease subgroups. The transcriptome of human cerebral ependymomas that amplify EPHB2 and delete INK4A/ARF matched most closely that of embryonic cerebral Ink4a/Arf-/- RG: remarkably, activation of EphB2 signaling in this RG type, but not others, generated highly penetrant ependymomas that modeled accurately the histology and transcriptome of one human cerebral tumor subgroup (subgroup D). Further comparative genomic analysis revealed selective alterations in the copy number and expression of genes that regulate neural differentiation, particularly synaptogenesis, in both mouse and human subgroup D ependymomas; pinpointing this pathway as a previously unknown target of ependymoma tumorigenesis. Our data demonstrate the power of comparative genomics to sift complex genetic data sets to identify key molecular alterations in cancer subgroups.
Publication Title
Cross-species genomics matches driver mutations and cell compartments to model ependymoma.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples