PFAPA, the syndrome of periodic fever associated with aphthous stomatitis, pharyngitis and/or cervical adenitis, is the most common periodic fever disease in children. Cases are mostly sporadic; the etiopathogenesis is unknown.
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) is a disorder of innate immunity and Th1 activation responsive to IL-1 blockade.
Sex, Age, Disease, Disease stage, Subject
View SamplesOncogene-induced senescence is an anti-proliferative stress response program that acts as a fail-safe mechanism to limit oncogenic transformation and is regulated by the retinoblastoma protein (RB) and p53 tumor suppressor pathways. We identify the atypical E2F family member E2F7 as the only E2F transcription factor potently upregulated during oncogene-induced senescence, a setting where it acts in response to p53 as a direct transcriptional target. Once induced, E2F7 binds and represses a series of E2F target genes and cooperates with RB to efficiently promote cell cycle arrest and limit oncogenic transformation. Disruption of RB triggers a further increase in E2F7, which induces a second cell cycle checkpoint that prevents unconstrained cell division despite aberrant DNA replication. Mechanistically, E2F7 compensates for the loss of RB in repressing mitotic E2F target genes.
The atypical E2F family member E2F7 couples the p53 and RB pathways during cellular senescence.
Cell line, Treatment
View SamplesWe identified Ncoa3 as a regulator of neuronal morphology and microRNA activity. In order to uncover target genes of this transcriptional coactivator we performed this microarray analysis.
A large-scale functional screen identifies Nova1 and Ncoa3 as regulators of neuronal miRNA function.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence.
Specimen part, Cell line
View SamplesCellular senescence is a tumor-suppressive program that involves chromatin reorganization and specific changes in gene expression that trigger an irreversible cell-cycle arrest. We have examined the effect of suppressing the histone demethylases Jarid1a and Jarid1b on the senescence-associated gene expression signatures.
H3K4 demethylation by Jarid1a and Jarid1b contributes to retinoblastoma-mediated gene silencing during cellular senescence.
Specimen part, Cell line
View SamplesDuring development, lineage specification is controlled by several signaling pathways involving various transcription factors (TFs). Here, we studied the RE1-silencing transcription factor (REST) and identified an important role of this TF in cardiac differentiation. Using mouse embryonic stem cells (ESC) to model development, we analyzed the effect of REST knock-out on the ability to these cells to differentiate into the cardiac lineage. Detailed analysis of specific lineage markers expression showed selective down-regulation of endoderm markers in REST-null cells, thus contributing to a loss of cardiogenic signals.
A Role for RE-1-Silencing Transcription Factor in Embryonic Stem Cells Cardiac Lineage Specification.
Specimen part, Treatment
View SamplesDifferential expression patterns of total mRNA in traditionally expanded T cells (vehicle) compared to T cells expanded under drugs (AKT inhibitor and CAL-101) Overall design: Comparison of transcriptional effects of two different drugs
PI3Kδ Inhibition Enhances the Antitumor Fitness of Adoptively Transferred CD8<sup>+</sup> T Cells.
Specimen part, Treatment, Subject
View SamplesT cells contribute to host-tumor interactions in patients with monoclonal gammopathies. Expansions of CD8+CD57+TCRV+ restricted cytotoxic T cell (CTL) clones are found in 48% of patients with multiple myeloma and confer a favorable prognosis. We now report the presence of CTL clones with varying TCRV repertoire in 70% of patients with Waldenstroms Macroglobulinaemia (WM) (n=20). Previous nucleoside analogue (NA) therapy, associated with an increased incidence of transformation to aggressive lymphoma, significantly influenced the presence of TCRV expansions (X2=11.6; P<0.001) as 83% of patients without (n=6) and only 7% with TCRV expansions (n=14) had received NA. Clonality of CD3+CD8+CD57+TCRV+ restricted CTLs were confirmed by TCRV CDR3 size analysis and direct sequencing. To characterize CTL clones, samples of CD3+CD8+CD57+TCRV+ cells were profiled using DNA microarrays and the results were validated on both gene and protein level. By gene set enrichment analysis, CTL clones not only expressed genes (GZMB, PRF1, FGFBP2) from cytotoxic pathways but also genes which suppress apoptosis, inhibit proliferation, arrest cell cycle G1/S transition and activate T cells (RAS, CSK and TOB pathways). Proliferation tracking confirmed their anergic state. Our studies demonstrate the incidence, NA sensitivity and anergic nature of clonal T cells in a B cell tumor.
Clonal expansions of cytotoxic T cells exist in the blood of patients with Waldenstrom macroglobulinemia but exhibit anergic properties and are eliminated by nucleoside analogue therapy.
Specimen part
View SamplesIn humans, the most common sex chromosomal disorder is Klinefelter syndrome (KS), caused by the presence of one or more extra X-chromosomes. The KS patients display a diverse adult phenotype with increased height, gynaecomastia, and hypergonadotropic hypogonadism as the most common symptoms. Men with KS are almost always infertile due to testicular degeneration, which accelerates during puberty. Very few studies investigated the global gene expression analysis of adult KS testes and, more importantly, which cell types the differentially expressed transcripts originate from. Transcriptome analysis by RNA sequencing of fixed and paraffin embedded testes originating from 3 adult KS samples and 3 adult cellularity-matched controls revealed 236 differentially expressed transcripts in the adult KS testis. To examine the cellular origin of the differentially expressed transcripts, transcriptome profiling was also carried out on 4 testes with Sertoli Cell-Only and 4 testes with full spermatogenesis. Also, pre-pubertal KS and controls were RNA-sequenced. Overall design: Includes a total of 22 testis samples. 3 adult Klinefelter, 3 Klinefelter-like, 4 Sertoli Cell-Only, 4 with full spermatogenesi, 4 pre-pubertal Klinefelter and 4 pre-pubertal controls
Transcriptome analysis of the adult human Klinefelter testis and cellularity-matched controls reveals disturbed differentiation of Sertoli- and Leydig cells.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Oct4 switches partnering from Sox2 to Sox17 to reinterpret the enhancer code and specify endoderm.
Cell line, Treatment
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