Conditional IRF8 KO mice (mice with a conditional allele of Irf8 crossed with CD19-Cre mice) showed increased numbers of both Gene expression data spleen marginal zone (MZ) and Gene expression data spleen follicular (FO) B cells compared to control mice.
IFN regulatory factor 8 restricts the size of the marginal zone and follicular B cell pools.
No sample metadata fields
View SamplesDendritic cells are the sentinels of the innate immune system. We used global microarray analysis to identify genes which are regulated by Toll-like receptor signaling pathways.
IRF8 directs stress-induced autophagy in macrophages and promotes clearance of Listeria monocytogenes.
Specimen part, Treatment
View SamplesThis study sought to evaluate the effects of dietary MeHg exposure on adult female yellow perch (Perca flavescens) and zebrafish (Danio rerio) reproduction by relating controlled exposures with subsequent reproductive effects. Yellow perch were used in the study for their socioeconomic and ecological importance within the Great Lakes basin, and the use of zebrafish allowed for a detailed analysis of the molecular effects of MeHg. MeHg exposures at environmentally relevant levels were done in zebrafish for a full life cycle, mimicking a realistic exposure scenario, and in adult yellow perch for twenty weeks, capturing early seasonal ovarian development. In zebrafish, several genes involved in reproductive processes were shown to be dysregulated by RNA-seq and QPCR, but no significant phenotypic or physiological changes were observed with ovarian staging, fecundity, or embryo mortality. Yellow perch did not appear to be affected by MeHg, either at a molecular level, as assessed by QPCR of eight genes in the pituitary, liver, and ovary tissue, or a physiological level, as seen with ovarian somatic index, circulating estradiol, and ovarian staging. Lack of impact in yellow perch limits the usefulness of zebrafish as a model and suggests that the reproductive sensitivity to environmentally relevant levels of MeHg differs between yellow perch and zebrafish. Overall design: 12 samples of total RNA isolated from adult zebrafish ovaries were analyzed. Each exposure group (1, 3, and 10 ppm MeHg) had three replicates, as did the vehicle control. Each sample was comprised of pooled total RNA of up to 6 individual fish.
Female reproductive impacts of dietary methylmercury in yellow perch (Perca flavescens) and zebrafish (Danio rerio).
No sample metadata fields
View SamplesMost human B cell lymphomas (B-NHL) are derived from germinal centers (GCs), the structure where B-cells undergo class switch recombination (CSR) and somatic hypermutation (SHM) and are selected for high-affinity antibody production. The pathogenesis of B-NHL is associated with distinct genetic lesions, including chromosomal translocations and aberrant somatic hypermutation, which appear to arise from mistakes occurring during CSR and SHM. To ascertain the role of CSR and SHM in lymphomagenesis, we crossed three oncogene-driven (MYC, BCL6, MYC/BCL6) mouse models of B cell lymphoma with mice lacking activation-induced cytidine deaminase (AID), the enzyme required for both processes.
AID is required for germinal center-derived lymphomagenesis.
Specimen part
View SamplesCarbonyl chloride (phosgene) is a toxic industrial compound (TIC) widely used in industry for the production of synthetic products, such as polyfoam rubber, plastics, and dyes. Exposure to phosgene results in a latent (1-24 hr), potentially life-threatening pulmonary edema and irreversible acute lung injury. A genomic approach was utilized to investigate the molecular mechanism of phosgene-induced lung injury. CD-1 male mice were exposed whole-body to either air or a concentration x time (c x t) amount of 32 mg/m3 (8 ppm) phosgene for 20 min (640 mg x min/m3). Lung tissue was collected from air- or phosgene-exposed mice at 0.5, 1, 4, 8, 12, 24, 48, and 72 hr post-exposure. RNA was extracted from the lung and used as starting material for the probing of oligonucleotide microarrays to determine changes in gene expression following phosgene exposure. The data were analyzed using principal component analysis (PCA) to determine the greatest sources of data variability. A three-way analysis of variance (ANOVA) based on exposure, time, and sample was performed to identify the genes most significantly changed as a result of phosgene exposure. These genes were rank ordered by p-values and categorized based on molecular function and biological process. Some of the most significant changes in gene expression reflect changes in glutathione synthesis and redox regulation of the cell, including upregulation of glutathione S-transferase alpha-2, glutathione peroxidase 2, and glutamate-cysteine ligase, catalytic subunit (also known as -glutamyl cysteine synthetase). This is in agreement with previous observations describing changes in redox enzyme activity after phosgene exposure. We are also investigating other pathways that are responsive to phosgene exposure to identify mechanisms of toxicity and potential therapeutic targets.
Genomic analysis of murine pulmonary tissue following carbonyl chloride inhalation.
No sample metadata fields
View SamplesDuring each life cycle germ cells preserve and pass on both genetic and epigenetic information. In C. elegans, the ALG-3/4 Argonaute (AGO) proteins and their small-RNA cofactors are expressed during male gametogenesis and promote male fertility. Here we show that the CSR-1 AGO functions with ALG-3/4 to positively regulate target genes required for spermiogenesis. Our findings suggest that ALG-3/4 functions during spermatogenesis to amplify a small-RNA signal that represents an epigenetic memory of male-specific gene expression, while CSR-1, which is abundant in mature sperm, transmits this memory to offspring. Surprisingly, in addition to small RNAs targeting male-specific genes, we show that males also harbor an extensive repertoire of CSR-1 small RNAs targeting oogenesis-specific mRNAs. Together these findings suggest that C. elegans sperm transmit not only the genome but also epigenetic binary signals in the form of Argonaute/small-RNA complexes that constitute a memory of which genes were active in preceding generations. Overall design: Examine small RNA changes in WT and alg-3/4 mutant males cultured at 20°C and 25°C, as well as determine the small RNAs enriched in a FLAG::CSR-1 IP from male worms grown at 25°C. mRNA sequencing was also performed to determine how transcripts targeted by small RNAs change in mutant background at 20°C and 25°C.
Argonautes promote male fertility and provide a paternal memory of germline gene expression in C. elegans.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.
Specimen part, Treatment
View SamplesThe unfolded protein response (UPR) maintains endoplasmic reticulum (ER) proteostasis through the activation of transcription factors such as XBP1s and ATF6. The functional consequences of these transcription factors for ER proteostasis remain poorly defined. Here, we describe methodology that enables orthogonal, small molecule-mediated activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the same cell independent of stress. We employ transcriptomics and quantitative proteomics to evaluate ER proteostasis network remodeling owing to the XBP1s and/or ATF6 transcriptional programs. Furthermore, we demonstrate that the three ER proteostasis environments accessible by activating XBP1s and/or ATF6 differentially influence the folding, trafficking, and degradation of destabilized ER client proteins without globally affecting the endogenous proteome. Our data reveal how the ER proteostasis network is remodeled by the XBP1s and/or ATF6 transcriptional programs at the molecular level and demonstrate the potential for selectively restoring aberrant ER proteostasis of pathologic, destabilized proteins through arm-selective UPR-activation.
Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.
Specimen part, Treatment
View SamplesThe unfolded protein response (UPR) maintains endoplasmic reticulum (ER) proteostasis through the activation of transcription factors such as XBP1s and ATF6. The functional consequences of these transcription factors for ER proteostasis remain poorly defined. Here, we describe methodology that enables orthogonal, small molecule-mediated activation of the UPR-associated transcription factors XBP1s and/or ATF6 in the same cell independent of stress. We employ transcriptomics and quantitative proteomics to evaluate ER proteostasis network remodeling owing to the XBP1s and/or ATF6 transcriptional programs. Furthermore, we demonstrate that the three ER proteostasis environments accessible by activating XBP1s and/or ATF6 differentially influence the folding, trafficking, and degradation of destabilized ER client proteins without globally affecting the endogenous proteome. Our data reveal how the ER proteostasis network is remodeled by the XBP1s and/or ATF6 transcriptional programs at the molecular level and demonstrate the potential for selectively restoring aberrant ER proteostasis of pathologic, destabilized proteins through arm-selective UPR-activation.
Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.
Specimen part, Treatment
View SamplesMale Sprague-dawley rats were exposed to saline, isopropyl alcohol, 1mg/kg, 3mg/kg or 6 mg/kg sulfur mustard for 30 min, 1 hr, 3 hr, 6 hr, or 24 hr before analysis of lung tissue by oligonucleotide array analysis.
Genomic analysis of rodent pulmonary tissue following bis-(2-chloroethyl) sulfide exposure.
No sample metadata fields
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