B cell chronic lymphocytic leukemia (CLL) is often preceded by a benign monoclonal or oligoclonal CD5+ B cell lymphocytosis. We have generated transgenic mice expressing a catalytically inactive, dominant-negative recombination activating gene 1 (dnRAG1 mice) in the periphery. These animals develop an early-onset indolent CD5+ B cell lymphocytosis, caused in part by a defect in secondary V(D)J rearrangements initiated to alter autoreactive B cell receptor specificity. Hypothesizing that the CD5+ B cells accumulating in dnRAG1 mice represent a CLL precursor, we crossed dnRAG1 mice with CLL-prone E-TCL1 mice to determine whether dnRAG1 expression in E-TCL1 mice accelerates the onset of CLL-like disease. We find that CD5+ B cell expansion and CLL progression occurs more rapidly and uniformly in double-transgenic mice (DTG mice) compared to E-TCL1 mice, but with similar phenotypic and leukemogenic features. To gain insight into genes or pathways responsible for CD5+ B cell accumulation in the transgenic mice, we performed comparative gene expression profiling studies using normal and CD5+ B cells isolated from wild-type and transgenic mice at either 12 weeks of age (pre-leukemia) or at CLL onset in DTG mice (using age-matched wild-type and single-transgenic mice as controls). These analyses confirm the upregulation of tolerogenic genes in CD5+ B cells and reveal a possible role for prolactin signaling in the regulation of receptor editing. This study suggests that a failure to remodel B cell antigen receptor genes in response to autoreactivity may promote the benign accumulation of CD5+ B cells, which may then be subjected to secondary genetic lesions that promote CLL progression.
Accelerated progression of chronic lymphocytic leukemia in Eμ-TCL1 mice expressing catalytically inactive RAG1.
Age, Specimen part
View SamplesMicroRNAs (miRNAs) are a class of short non-coding RNA that play important roles in disease processes in animals and are present in a highly stable cell-free form in body fluids. Here we examine the capacity of host and parasite miRNAs to serve as tissue or serum biomarkers of Schistosoma mansoni infection. Sequencing of small RNAs from serum confirmed the presence of miRNAs and revealed 11 parasite-derived miRNAs that were detectable by 8 weeks post S.mansoni infection. Overall design: Small RNA content in serum of naïve and Schistosoma mansoni infected mice were examined in two different librarys. 1- prepared according to the 290 Illumina small RNA Sample Preparation Kit version 1.5 and sequenced on the GAIIX and 2- prepared according to the TruSeq Small RNA protocol (without size-selecting small 295 RNA) and sequenced on the HiSeq2
Parasite-derived microRNAs in host serum as novel biomarkers of helminth infection.
Sex, Cell line, Subject
View SamplesWe report that cellular ROS enzymatically generated in response to contact with lactobacilli in both mice and Drosophila has salutary effects against exogenous insults to the intestinal epithelium via the activation of Nrf2 responsive cytoprotective genes. Overall design: RNA was isolated from the colons of untreated, PBS, E. coli, and LGG innoculated germ free mice and RNA-seq performed to identify the gene expression in response to each condition
Lactobacillus rhamnosus GG-induced Expression of Leptin in the Intestine Orchestrates Epithelial Cell Proliferation.
Age, Specimen part, Cell line, Subject
View SamplesDose-dependent femoral gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the femur of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
2,3,7,8-Tetrachlorodibenzo-p-dioxin dose-dependently increases bone mass and decreases marrow adiposity in juvenile mice.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesDose-dependent ileal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.
Sex, Cell line, Treatment, Subject
View SamplesDose-dependent duodenal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesDose-dependent hepatic gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the liver of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesThe HT29 derivative cell line HT29-MTX-E12 (E12) produces an adherent mucus layer predominantly of the gastric MUC5AC mucin when grown on transwells. This mucus layer supports Helicobacter pylori survival in culture. E12 cells were infected with H. pylori and the transcriptome of infected and uninfected E12 were compared. Also included for comparison was the HT29 parent cell line grown on transwells.
Glycosylation-related gene expression in HT29-MTX-E12 cells upon infection by <i>Helicobacter pylori</i>.
Cell line
View SamplesFetal liver of E14.5 RNaseh2b KOF and Rnaseh2b wild type embryos was isolated, RNA was extracted and microarray analysis using Affymetrix Mouse 430 2.0 gene chip was performed
Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity.
Specimen part
View SamplesAg recognition via the TCR is necessary for the expansion of specific T cells that then contribute to adaptive immunity as effector and memory cells. Because CD4+ and CD8+ T cells differ in terms of their priming APCs and MHC ligands we compared their requirements of Ag persistence during their expansion phase side by side. Proliferation and effector differentiation of TCR transgenic and polyclonal mouse T cells were thus analyzed after transient and continuous TCR signals. Following equally strong stimulation, CD4+ T cell proliferation depended on prolonged Ag presence, whereas CD8+ T cells were able to divide and differentiate into effector cells despite discontinued Ag presentation. CD4+ T cell proliferation was neither affected by Th lineage or memory differentiation nor blocked by coinhibitory signals or missing inflammatory stimuli. Continued CD8+ T cell proliferation was truly independent of self-peptide/MHC-derived signals. The subset divergence was also illustrated by surprisingly broad transcriptional differences supporting a stronger propensity of CD8+ T cells to programmed expansion. These T cell data indicate an intrinsic difference between CD4+ and CD8+ T cells regarding the processing of TCR signals for proliferation. We also found that the presentation of a MHC class IIrestricted peptide is more efficiently prolonged by dendritic cell activation in vivo than a class I bound one. In summary, our data demonstrate that CD4+ T cells require continuous stimulation for clonal expansion, whereas CD8+ T cells can divide following a much shorter TCR signal.
Differential kinetics of antigen dependency of CD4+ and CD8+ T cells.
Specimen part, Treatment
View Samples