Most adult patients have a D816V mutation in phosphotransferase domain (PTD), we have described that half of the children carry mutations in extracellular domain (ECD). KIT-ECD versus IT-PTD-mutants were introduced into rodent Ba/F3, EML, Rat2 and human TF1 cells to investigate their biological effect. ECD- and PTD-mutants also displayed distinct whole-genome transcriptional profiles in EML cells. We observed differences in their signaling properties: they both activated STAT pathways, whereas AKT pathway was only activated by ECD-mutants. Consistently, AKT inhibitor suppressed ECD-mutant-dependent proliferation, clonogenicity and erythroid differentiation. Expression of myristoylated AKT restored erythroid differentiation in EMLPTD cells, suggesting the differential role of AKT in those mutants. Overall, our study implied different pathogenesis of pediatric versus adult mastocytosis, which might explain their diverse phenotypes.
Pediatric mastocytosis-associated KIT extracellular domain mutations exhibit different functional and signaling properties compared with KIT-phosphotransferase domain mutations.
Cell line, Time
View SamplesFAN (Factor associated with neutral sphingomyelinase activation) is an adaptor protein that constitutively binds to TNF-R1. Microarray analysis was performed in fibroblasts derived from wild-type or FAN knockout mouse embryos to evaluate the role of FAN in TNF-induced gene expression.
FAN stimulates TNF(alpha)-induced gene expression, leukocyte recruitment, and humoral response.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reprogramming factor expression initiates widespread targeted chromatin remodeling.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sequentially acting Sox transcription factors in neural lineage development.
Specimen part
View SamplesWe report sequential binding but unique functions of different Sox transcription factors during distinct stages of neural differentiation
Sequentially acting Sox transcription factors in neural lineage development.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional signatures of Itk-deficient CD3+, CD4+ and CD8+ T-cells.
No sample metadata fields
View SamplesSmall RNAs, such as miRNAs and siRNAs, are involved in gene regulation in a variety of systems, including mouse oocytes. Dicer is a ribonuclease III enzyme essential for miRNA and siRNA biosynthesis. In an effort to uncover the function of small RNAs during oocyte growth, we specifically deleted Dicer in growing oocytes and analyzed the global pattern of gene expression in these Dicer-deficient oocytes.
MicroRNA activity is suppressed in mouse oocytes.
Sex, Specimen part
View SamplesNotch signaling regulates a variety of developmental cell fates decisions in a cell-context dependent manner. Although Notch signaling directly regulates transcription via the RBP-J/CSL DNA binding protein, little is known about the genes in the respective tissues that are directly activated by Notch.
Activated Notch1 target genes during embryonic cell differentiation depend on the cellular context and include lineage determinants and inhibitors.
Specimen part
View SamplesInappropriate excess of the steroid hormone aldosterone, which is a mineralocorticoid receptor (MR) agonist, is associated with increased inflammation and risk of cardiovascular disease. MR antagonists are cardioprotective and antiinflammatory in vivo, and evidence suggests that they mediate these effects in part by aldosterone- independent mechanisms.
Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice.
Sex, Specimen part, Treatment
View SamplesExpression profiles generated during dissection of the molecular mechanisms underlying direct reprogramming of somatic cells to a pluripotent state (induced pluripotent stem cells, iPS).
Dissecting direct reprogramming through integrative genomic analysis.
No sample metadata fields
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