IKK kinase is essential for the B cell maturation and secondary lymphoid organ development. In the current study, we evaluated the role of IKK in the marginal zone and follicular B lymphocyte development by genetically deleting IKK from the B cell lineage using CD19-Cre mice. The loss of IKK did not affect the normal development of early B cell progenitors. However, a significant decline was observed in the percentage of immature B lymphocytes, mature marginal zone and follicular B cells along with a severe disruption of splenic marginal and follicular B cell zones. A gene expression analysis performed on the RNA extracted from the newly formed B cells (B220+IgMhi) revealed that IKK deficiency produces significant changes in the expression of genes involved in MZ and FO B lymphocyte survival, homing and migration. And several among those genes identified belong to G protein family. Specifically, we validated the upregulated expression of regulator of G protein signaling 13 (RGS13), which is a GTPase activating protein (GAP) that negatively regulates G protein signaling and impede B cell migration. Likewise, promigratory B lymphocyte receptor, the sphingosine-1-phosphate receptor 3 (SIPR3) that couple to Gi showed significantly reduced expression. In addition, an in silico analysis of gene product interactions revealed NF-B signaling pathways to be a major gene regulating networks perturbed with IKK deletion. Taken together, this study reveals IKKNF-B and G protein signaling axis to be central for the MZ and FO B cells survival, maintenance, homing and migration.
IKKα deficiency disrupts the development of marginal zone and follicular B cells.
Specimen part
View SamplesBoth pro- and anti-mitogenic activities have been ascribed to progesterone receptor (PR) agonists and antagonists in breast cancer cells, however, the transcriptional responses that underlie these paradoxical functions are not apparent. Using non-transformed, normal human mammary epithelial cells (hMECs) engineered to express PR, and standard microarray technology, we defined 2,370 genes that were significantly regulated by the PR agonist R5020. Gene Ontology (GO) analysis revealed that GO-terms involved in inflammation and NF-B signaling were among the most significantly regulated. Interestingly, on those NF-B responsive genes that were inhibited by agonist-activated PR, antagonists either (a) mimicked the actions of agonists or (b) reversed the inhibitory actions of agonists. This difference in pharmacological response could be attributed to the fact that although agonist and antagonist-activated PR is recruited to the promoters of NF-B responsive promoters, the physical presence of PR tethered to the promoter of some genes is sufficient for transcriptional inhibition whereas on others an agonist-activated PR conformation is required for inhibition of NF-B signaling. Importantly, the actions of PR on the latter class of genes were reversed by an AF-2 inhibiting, LXXLL-containing peptide. Consideration of the relative activities of these distinct anti-inflammatory pathways in breast cancer may be instructive with respect to the likely therapeutic activity of PR agonists or antagonists in the treatment of breast cancer.
Mechanisms of progesterone receptor inhibition of inflammatory responses in cellular models of breast cancer.
Specimen part
View SamplesWe prepared small RNA libraries from 29 tumor/normal pairs of human cervical tissue samples. Analysis of the resulting sequences (42 million in total) defined 64 new human microRNA (miRNA) genes. Both arms of the hairpin precursor were observed in twenty-three of the newly identified miRNA candidates. We tested several computational approaches for analysis of class differences between high throughput sequencing datasets, and describe a novel application of log linear model that has provided the most datasets, and describe a novel application of log linear model that has provided the most effective analysis for this data. This method resulted in the identification of 67 miRNAs that were differentially-expressed between the tumor and normal samples at a false discovery rate less than 0.001. Overall design: A total of 29 tumor/normal pairs of human cervical tissue samples were analyzed. Two samples (G699N_2 and G761T_2) were performed in duplicates. No Fastq files for GSM532871 to GSM532889, GSM532929, and GSM532930. Sequence files are provided as text files for these 22 Sample records in GSE20592_RAW.tar. 38 samples with quality scores are available from SRA as SRP002/SRP002326 (see Supplementary file below).
Ultra-high throughput sequencing-based small RNA discovery and discrete statistical biomarker analysis in a collection of cervical tumours and matched controls.
No sample metadata fields
View SamplesGene expression (mRNA) profiling of human ependymomas
Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma.
Sex, Age, Specimen part
View SamplesThe selective impact of pathogen epidemics on host defenses can be strong but remains transient. By contrast, life-history shifts can durably and continuously modify the balance between costs and benefits, which arbitrates the evolution of host defenses. Their impact, however, has seldom been documented. Here, we show with a simple mathematical model that the selective advantage of the defense system is expected to decrease with decreasing life span. We further document that, in natural populations of the model plant system Arabidopsis thaliana, the expression level of defense genes correlate positively with flowering time, a proxy for the length of vegetative life span. Using a genetic strategy to partition life span-dependent and –independent defense genes, we demonstrate that this positive co-variation is not explained by the pleiotropic action of major regulatory genes controlling both defense and life span. In agreement with our model, this study reveals that natural selection has likely assembled alleles promoting lower expression of defense genes with alleles decreasing the duration of vegetative life span in natural populations of A. thaliana. This is the first study demonstrating that life history evolution has a pervasive impact on the evolution of host immunity. Overall design: Seeds of Bur-0, Col-0 and 278 Bur-0xCol-0 Recombinant Inbred Lines (RIL) obtained after 8 generations of selfing were provided by the Arabidopsis Stock Center at INRA Versailles (France). We selected the 40 RIL in the 15% and 85% quantiles of flowering time for RNA sequencing. Each RIL and the two parental lines were planted in 20 replicates in the conditions described above. At days 14 and 28, the oldest leaf was flash-frozen in liquid nitrogen. Three pools, each combining 13 RIL, were produced at each time point for early and late lines, for a total of 3 biological replicates, 2 pool types (early and late RIL) and 2 time points (14 and 28 days). For each of the two parental lines, leaves of 12 replicates were pooled for each time point.
Assortment of Flowering Time and Immunity Alleles in Natural Arabidopsis thaliana Populations Suggests Immunity and Vegetative Lifespan Strategies Coevolve.
Specimen part, Subject, Time
View SamplesDifferential gene expression between naive and activated CD8+ T cells was assessed using microarray analysis to determine target genes for new positron emission tomography (PET) probe screening, in particular for molecular imaging of lymphoid organs and immune activation.
Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2'-deoxycytidine analog.
No sample metadata fields
View SamplesStudy of the gene expression of T24 bladder cancer cells in response to hypericin-mediated photodynamic therapy in the absence or presence of the p38 MAPK inhibitor PD169316
Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells.
None
Specimen part, Cell line, Compound
View SamplesThe transcriptional response of Arabidopsis thaliana cell suspensions following treatment with the stress hormone methyl jasmonate (MeJA) was monitored over time 16 hours after subcultivation. Three time points were included: 30 minutes, 2 hours and 6 hours after elicitation with 50µm MeJA or DMSO as a control.
Mapping methyl jasmonate-mediated transcriptional reprogramming of metabolism and cell cycle progression in cultured Arabidopsis cells.
None
Compound, Time
View SamplesGene expression profiles of bipolar disorder (BD) patients were assessed during both a manic and a euthymic phase and compared both intra-individually, and with the gene expression profiles of controls.
Investigation of manic and euthymic episodes identifies state- and trait-specific gene expression and STAB1 as a new candidate gene for bipolar disorder.
Specimen part, Disease, Subject
View SamplesProsaposin encodes, in tandem, four small acidic activator proteins (saposins) with specificities for glycosphingolipids hydrolases in lysosomes. To explore the molecular mechanism(s) of disease progression, temporal transcriptome microarray analyses of cerebrum and cerebellum tissues were conducted using mRNA from three prosaposin deficiency mouse models: PS-NA (hypomorphic prosaposin deficiency), PS-/- (prosaposin null) and 4L/PS-NA (a V394L/V394L glucocerebrosidase mutation and PS-NA) mice. Our results indicate that regionally specific gene expression abnormalities preceded the histological and behavioral changes and CEBPD is a candidate regulator of brain disease in prosaposin deficiency. The alterations of gene expression are detected at birth and are more profound in cerebellum than cerebrum.
Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice.
No sample metadata fields
View Samples