The 24R,25-dihydroxyvitamin D metabolite (24R,25D) has long been suspected of participating to bone fracture repair. We used Cyp24a1-deficient mice, unable to produce 24R25D, to observe gene expression in callus tissue compared to that of control littermates.
Optimal bone fracture repair requires 24R,25-dihydroxyvitamin D3 and its effector molecule FAM57B2.
Age, Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Medulloblastoma subgroups remain stable across primary and metastatic compartments.
Sex, Age, Specimen part, Subject
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Peripheral Nerve Single-Cell Analysis Identifies Mesenchymal Ligands that Promote Axonal Growth.
Sex, Specimen part, Treatment
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Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair.
Treatment
View SamplesAffymetrix Human Gene 2.0 ST Array profiling of 9 pairs of matched primary-metastases medulloblastoma samples.
Medulloblastoma subgroups remain stable across primary and metastatic compartments.
Sex, Age, Specimen part, Subject
View SamplesStress granules are small RNA-protein granules that modify the translational landscape during cellular stress to promote survival. The RhoGTPase RhoA is implicated in the formation of RNA stress granules. Our data demonstrate that the cytokinetic proteins ECT2 and AurkB are localized to stress granules in human astrocytoma cells. AurkB and its downstream target histone-3 are phosphorylated during arsenite-induced stress. Chemical (AZD1152-HQPA) and siRNA inhibition of AurkB results in fewer and smaller stress granules when analyzed utilizing high throughput fluorescent based cellomics assays. RNA immunoprecipitation with the known stress granule aggregates TIAR and G3BP1 was performed on astrocytoma cells and subsequent analysis revealed that astrocytoma stress granules harbour unique mRNAs for various cellular pathways including cellular migration, metabolism, translation and transcriptional regulation. Human astrocytoma cell stress granules contain mRNA that are known to be involved in glioma signaling and the mTOR pathway. These data provide evidence that RNA stress granules are a novel form of epigenetic regulation in astrocytoma cells, which may be targetable by chemical inhibitors and enhance astrocytoma susceptiblity to conventional therapy such as radiation and chemotherapy.
Epithelial Cell Transforming 2 and Aurora Kinase B Modulate Formation of Stress Granule-Containing Transcripts from Diverse Cellular Pathways in Astrocytoma Cells.
Specimen part, Cell line
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Direct genesis of functional rodent and human schwann cells from skin mesenchymal precursors.
Specimen part
View SamplesAlthough anemia is common in Shwachman-Diamond syndrome (SDS), the underlying mechanism remains unclear. We asked whether SBDS, which is mutated in most SDS patients, is critical for erythroid development. We found that SBDS expression is high early during erythroid differentiation. Inhibition of SBDS in CD34+ hematopoietic stem cells and early progenitors (HSC/Ps) and K562 cells led to slow cell expansion during erythroid differentiation. Induction of erythroid differentiation resulted in markedly accelerated apoptosis in the knockdown cells; however, proliferation was only mildly reduced. The percentage of cells entering differentiation was not reduced.
The ribosome-related protein, SBDS, is critical for normal erythropoiesis.
Specimen part, Disease, Disease stage
View SamplesExpression of the Endothelin-2 (Edn2) mRNA is greatly increased in the photoreceptors (PRs) of mouse models of inherited PR degeneration. To identify retinasl gene whose expression is directly or indirectly regulated by EDN2 in the presence of the Tg(RHO P347S) mutant allele, we defined mRNAs that were differentially expressed in Edn2+/+, Edn2-/-, Tg(RHO P347S) Edn2+/+, and Tg(RHO P347S) Edn2-/- retinas.
No associated publication
Specimen part
View SamplesMetastatic relapse is the major cause of death in neuroblastoma (NB), yet there are no therapies to specifically target metastases. To understand the molecular mechanisms mediating NB metastasis, we developed a mouse model using intracardiac injection and in vivo selection to isolate metastatic subpopulations that exhibited a higher propensity for bone and central nervous system metastases. Gene expression profiling revealed two distinct subtypes, primary and metastatic, with differential regulation of 412 genes and multiple pathways including CADM1, SPHK1, and YAP/TAZ whose expression independently predicted survival. Loss- and gain-of-function experiments with these genes demonstrated a rescue of metastatic phenotypes in multiple NB cell lines in vitro or in vivo. Treatment with the compounds SKI II and Verteporfin that target SPHK1 and YAP/TAZ, respectively, inhibited NB metastasis in vivo. In addition, using gene expression profiling from the metastatic subpopulations, a gene signature (MET-75) was identified that predicts NB survival of patients with metastatic disease. This model therefore identifies genes regulating metastasis and candidate therapeutics for metastatic NB
A Metastatic Mouse Model Identifies Genes That Regulate Neuroblastoma Metastasis.
Disease
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