Tumor necrosis factor-associated factors 2 and 3 (TRAF2 and TRAF3) were shown to function in a co-operative and non-redundant manner to suppress nuclear factor-B2 (NF-B2) activation, gene expression and survival in mature B cells. In the absence of this suppressive activity, B cells developed independently of the obligatory B cell survival factor, BAFF (B cell activating factor of the tumor necrosis factor family). This constitutive, lineage-specific suppression of B cell survival by TRAF2 and TRAF3 determines the requirement for BAFF to sustain B cell development in vivo. We wished to investigate the effect on gene expression in B cells which lacked the negative regulators TRAF2 and TRAF3, and hence had hyperactive NF-kB2 signalling. As Baff-tg mice display a similar phenotype, and have a genetic modification which acts in the same pathway, yet further up, than TRAF2 and TRAF3, we wished to compare and contrast Baff-tg B cells with TRAF2 and TRAF3 deficient B cells. This analysis should identify genes that are important in B cell survival.
TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor.
Sex, Age
View SamplesDrosophila S2 cells treated with either GFP or spottes-dick dsRNA and incubated for 5 days. There are three replicates for each condition.
Spotted-dick, a zinc-finger protein of Drosophila required for expression of Orc4 and S phase.
No sample metadata fields
View SamplesResistance to proteasome inhibitors (PIs) is a ubiquitous clinical concern in multiple myeloma (MM). We proposed that signaling-level responses after PI would reveal new means to enhance efficacy. Unbiased phosphoproteomics after the PI carfilzomib surprisingly demonstrated the most prominent phosphorylation changes on spliceosome components. Spliceosome modulation was invisible to RNA or protein abundance alone. Transcriptome analysis demonstrated broad-scale intron retention suggestive of PI-specific splicing interference. Direct spliceosome inhibition synergized with carfilzomib and showed potent anti-myeloma activity. Functional genomics and exome sequencing further supported the spliceosome as a specific vulnerabilityin myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma. Overall design: We examine 1) gene expression of MM cells in response to PI and 2)alternative splicing in response to PI and comparator chemotherapeutic compound. We further investigate splice factor mechanism in MM cells, by examining alternative splicing in MM with overexpression of wild type and mutant splice factor, SRSF1
Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma.
Cell line, Subject, Compound, Time
View SamplesDnmt3b is a DNA methytransferase which is an enzyme that methylated genomic DNA which contributes to genomic stability and transcriptional regulation.
Loss of Dnmt3b function upregulates the tumor modifier Ment and accelerates mouse lymphomagenesis.
Specimen part
View SamplesHuman oviduct serves as a conduit for sperm in the peri-ovulatory phase and to nurture and facilitate transport of the developing embryo en route to the uterus for subsequent nidation during the luteal phase of the cycle. Interactions between the embryo and oviductal epithelial surface proteins and secreted products during the four day embryo transit are largely undefined. Herein, we have investigated gene expression in human oviduct in the early luteal vs. follicular phase to identify candidate genes and biomolecular processes that may participate in maturation and transport of the embryo as it traverses this tissue. Oviductal RNA was isolated, processed, and hybridized to oligonucleotide arrays. Resulting data were analyzed by bioinformatic approaches and revealed that 650 genes were significantly downregulated and 683 genes were significantly upregulated in the luteal vs. follicular phase. Real-time RT-PCR, immunoblot analysis, and immunohistochemistry confirmed select gene expression and cellular protein localization. The data demonstrate downregulation of genes involved in macrophage recruitment, immunomodulation, and matrix-degeneration and upregulation of ion transport and secretions as well as anti-angiogenic and early pregnancy recognition genes in luteal vs. follicular phase oviduct. Together, these data suggest a unique hormonally regulated environment during embryo development, maturation and transport through human oviduct.
The human oviduct transcriptome reveals an anti-inflammatory, anti-angiogenic, secretory and matrix-stable environment during embryo transit.
Specimen part
View SamplesGene expression analysis performed on FACS sort purified GC LZ and DZ cells of either high or low affinity to identify unique gene signatures.
Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells.
Sex, Specimen part
View SamplesGene expression analysis performed on FACS sort purified GC LZ and DZ cells of either high and low affinity to identify unique gene signatures.
Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells.
Sex, Specimen part
View SamplesPurpose: The goal of this study is to compare the differential expression of transcripts in control kidneys compared to kidneys lacking the miR-17~92 cluster in nephron progenitors and their derivatives by RNA-seq to identify potential miRNA targets in the mutant kidneys. Overall design: mRNA profiles of control and mutant (=Six2-TGC; miR-17~92 flx/flx) embryonic day 16 kidneys were generated by deep sequencing, in triplicate, using Illumina HiSeq2000
MicroRNA-17~92 is required for nephrogenesis and renal function.
No sample metadata fields
View SamplesTo study mechanisms of long bone growth regulation, p21 misexpression was induced in the left hindlimb of mouse embryos using an intersectional approach that requires both Cre and (r)tTA activity. Doxycycline was provided to the pregnant female at embryonic day (E)12.5 to activate the transgene, and embryos were collected at E17.5. Distal femur and proximal tibia growth plates were dissected out, keeping left and right separated, deprived of perichondrium and flash frozen. After RNA extraction, mRNA libraries were prepared and all samples were deep sequenced in parallel Overall design: 6 samples (left and right growth plates from embryos #386, #387, #388) were sequenced in parallel
Cell-nonautonomous local and systemic responses to cell arrest enable long-bone catch-up growth in developing mice.
Specimen part, Subject
View SamplesRNA expression was measured by RNA-seq in E17 wild type and Sall1-?SRM mutant kidney. Overall design: RNA expression in mutant kidney was compared to wild type stage matched kidney.
A Sall1-NuRD interaction regulates multipotent nephron progenitors and is required for loop of Henle formation.
Specimen part, Subject
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