Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, genetically heterogeneous autosomal recessive immune disorder that results when the critical regulatory pathways that mediate immune defense mechanisms and the natural termination of immune/inflammatory responses are disrupted or overwhelmed. In order to advance the understanding of FHL, we performed gene expression profiling of peripheral blood mononuclear cells (PBMCs) from 11 children with untreated FHL. Total RNA was isolated and gene expression levels were determined using microarray analysis. Comparisons between patients with FHL and normal pediatric controls (n = 30) identified 915 down-regulated and 550 up-regulated genes with 2.5-fold difference in expression (P = 0.05). The expression of genes associated with natural killer cell functions, innate and adaptive immune responses, pro-apoptotic proteins, and B- and T-cell differentiation were down-regulated in patients with FHL. Genes associated with the canonical pathways of IL-6, IL-10 IL-1, IL-8, TREM1, LXR/RXR activation, and PPAR signaling and genes encoding of anti-apoptotic proteins were overexpressed in patients with FHL. This, first study of genome-wide expression profiling in children with FHL demonstrates the complexity of gene expression patterns, which underly the immunobiology of FHL.
Gene expression profiling of peripheral blood mononuclear cells from children with active hemophagocytic lymphohistiocytosis.
Specimen part
View SamplesA total number of 1,511 probe sets in the bone marrow showed at least two-fold changes with FDR < 0.05, of which 256 probe sets had over four-fold changes. A group of 63 genes in the bone marrow of NDLD mice had more than a 4-fold change with FDR < 0.0001. From 503 genes encoding proteins with ITIM motif that binds to Ptpn6, 109 were up-regulated and 83 were down-regulated.
A differential gene expression study: Ptpn6 (SHP-1)-insufficiency leads to neutrophilic dermatosis-like disease (NDLD) in mice.
Disease, Disease stage
View SamplesThe regulatory subunit of cAMP-dependent protein kinase (PKA) exists in two isoforms, RI and RII, which distinguish the PKA isozymes, type I (PKA-I) and type II (PKA-II). Evidence obtained from a variety of different experimental approaches has shown that the relative levels of type I and type II PKA in cells can play a major role in determining the balance between cell growth and differentiation. RI transfected cells exhibit hyper-proliferative growth and RII transfected cells revert to a relatively quiescent state. Profiling by microarray revealed equally profound changes in gene expression between RI, RII, and parental OVCAR cells.
Regulatory subunits of PKA define an axis of cellular proliferation/differentiation in ovarian cancer cells.
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View SamplesDifferent osteoprogenitors (SSC, BCSP, Thy+) were sorted after 2 days of JUN induction, followed by RNA extraction and microarray analysis
Expansion of Bone Precursors through Jun as a Novel Treatment for Osteoporosis-Associated Fractures.
Specimen part
View SamplesTime course analysis of c-Jun expression at 24h resulted in upregulation of a number of well-known fibrogenesis-associated factors.
Unifying mechanism for different fibrotic diseases.
Specimen part
View SamplesBcl11b plays an important role in postnatal dentate gyrus development and adult neurogenesis. To determine its role in adult neurogenesis independant from postnatal development the Bcl11b mutation was induced at the age of 2 months.
Stability and Function of Hippocampal Mossy Fiber Synapses Depend on <i>Bcl11b/Ctip2</i>.
Specimen part
View SamplesIn this study we investigate the role of the non-canonical SMC family protein, SmcHD1in the X inactivation. Overall design: Set of allele-specific chromatin RNA-seq experiments on female clonal inter-specific (M.m.domesticus FVB x M.m.Castaneus) MEF cell lines: wild-type MEFs, SmcHD1 MomeD1 mut MEFs (SmcHD1 null) and SmcHD1 CRISPR KO MEFs (derived from wild-type MEFs after establishemnt of X inactivation).
The non-canonical SMC protein SmcHD1 antagonises TAD formation and compartmentalisation on the inactive X chromosome.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells.
Specimen part
View SamplesDNA methylation is the net result of deposition by DNA methyltransferases (DNMT1, 3A and 3B) and removal by the Ten-Eleven Translocation 1-3 (TET1-3) family of proteins and/or passive loss by replication. The relative contribution of the individual enzymes and pathways is only partially understood. Here we comprehensively analyzed and mathematically simulated the dynamics of DNA de-methylation during the reprogramming of the hypermethylated serum-cultured mouse embryonic stem cells (ESCs) to the hypomethylated 2i-cultured ground state of mESC. We show that DNA demethylation readily occurs in TET[1-/-, 2-/-] ESCs with similar kinetics as their WT littermates. Vitamin C activation of TET causes accelerated and more profound DNA demethylation without markedly affecting reprogramming kinetics. We developed a mathematical model that highly accurately predicts the global level of 5methyl- and 5hydroxymethylcytosine during the transition. Modeling and experimental validation show that the concentration of DNMT3A and DNMT3B determines the steady state level of global DNA methylation and absence of DNMT3A/B even in continued presence of DNMT1 results in gradual loss of 5mC. Taken together, DNMT1 alone is insufficient to maintain DNA methylation but requires the action of DNMT3A/3B that act as a “dimmer switches”. Overall design: RNA-seq time series was performed during the early time phase of serum to 2i transition in the presence and absence of vitamin C (4h, 16h,24h, 32h), 1 replicate
Impairment of DNA Methylation Maintenance Is the Main Cause of Global Demethylation in Naive Embryonic Stem Cells.
No sample metadata fields
View SamplesThe protein Dicer is required for microRNA (miRNA) biogenesis. Dicer-deficient cells therefore lack almost all mature, functional miRNAs. We investigated the role of miRNAs in regulation of gene expression in mouse
MicroRNAs of the miR-290-295 Family Maintain Bivalency in Mouse Embryonic Stem Cells.
Specimen part
View Samples