To investigate how the phenotype of macrophages that have engulfed engineered nanoparticles (ENPs) differs from normal macrophages, we conducted Affymetrix microarray studies to identify the gene regulatory pathways affected by the ENPs. To mimic potential occupational exposure scenarios, the experimental design involved pretreatment of mouse primary bone marrow macrophages with the ENPs (25 mg/ml) for 24 hr, followed by removal of residual ENPs and challenging the macrophages with the TLR4 ligand and surrogate bacterial stimulus, lipopolysachharide (LPS) for 4 hr. The 4 hr challenge time was chosen based on preliminary studies which showed many of the proinflammatory gene expression responses peak between 2-6 hr after LPS treatment.
Dysregulation of macrophage activation profiles by engineered nanoparticles.
Specimen part, Treatment
View SamplesUsing a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles.
Macrophage responses to silica nanoparticles are highly conserved across particle sizes.
No sample metadata fields
View SamplesWe report the application of Illumina small RNA sequencing to normal human skin, as well as uninvolved and involved psoriatic skin. By obtaining over 600 million qualified reads from 20 healthy controls and 47 psoriasis biopsies (uninvolved/involved), we have generated a complete small RNA profile in normal and diseased human skin, with particular emphasis on miRNAs. We report the discovery of 284 putative novel miRNAs as well as 98 differentially expressed miRNAs in psoriatic skin. Overall design: miRNA discovery and expression profiling in 67 normal and psoriatic human skin biopsies
Deep sequencing of small RNAs from human skin reveals major alterations in the psoriasis miRNAome.
Specimen part, Disease, Disease stage, Subject
View SamplesGene expression data from VHL teratomas comparing genes differentially expressed based on apoptotic response to tumor microenvironment.
Pleiotropic effects of the trichloroethylene-associated P81S VHL mutation on metabolism, apoptosis, and ATM-mediated DNA damage response.
Specimen part
View SamplesHSF1 is a major transcriptional regulator of heat shock responses. Many cells activate HSF1 in response to heat shock temperatures (>42oC) and other cellular stress causing agents. Unlike other cell types, T cells activate HSF1 in response to T cell activation or when exposed to febrile (40oC) temperatures, suggesting a role for HSF1 beyond the heat-shock response.
Heat shock transcription factor 1 is activated as a consequence of lymphocyte activation and regulates a major proteostasis network in T cells critical for cell division during stress.
Specimen part, Treatment
View SamplesPurpose: We investigated the tetrachloroethylene associated changes in kidney transcriptomes among healthy mice, nonalcoholic fatty liver disease mice, and nonalcoholic steatohepatitis mice. Overall design: Male C57BL/6J mice were fed a low-fat diet (4% fat), high-fat diet (31% fat), or methionine/choline/folate deficient diet. Following an 8-week diet, mice were administered either a single dose of tetrachloroethylene (PERC, 300 mg/kg/d in 5% Alkamuls-EL620 in saline, 5 mL/kg) and euthanized at 24 hours post dose, or five consecutive daily doses of PERC or vehicle (n=8/diet/treatment) and euthanized at 4hours post dose. The harvested kidneys were subjected to mRNA sequencing using Illumina Hiseq 2500. Jac-NASH-063 was excluded from analysis because it did not have a good yield.
Modulation of Tetrachloroethylene-Associated Kidney Effects by Nonalcoholic Fatty Liver or Steatohepatitis in Male C57BL/6J Mice.
Cell line, Treatment, Subject
View SamplesMononuclear cells were isolated from the sternal bone marrow and prepared for multiparametric flow cytometry using an optimized and validated protocol. B-cell subsets of PreBI, PreBII, Immature, Naive, Memory and Plasma cells were isolated and a al of 38 gene expression profiles were generated using the HuEx-1_0-st-v2-micro array chip from Affymetrix to characterize the gene expression in the individual subpopulations.
Long Noncoding RNA Expression during Human B-Cell Development.
Specimen part, Subject
View SamplesLong noncoding RNAs (lncRNAs) have emerged as important regulators of diverse cellular processes, but their roles in the developing immune system are poorly understood. In this study, we analysed lncRNA expression during human B-cell development by array-based expression profiling of eleven distinct flow-sorted B-cell subsets, comprising pre-B1, pre-B2, immature, naive, memory, and plasma cells from bone marrow biopsies (n=7), and naive, centroblast, centrocyte, memory, and plasmablast cells from tonsil tissue samples (n=6), respectively. A remapping strategy was used to assign the array probes to 37630 gene-level probe sets, reflecting the most recent updates in genomic and transcriptomic databases, which enabled expression profiling of 19579 long noncoding RNAs, comprising 3947 antisense RNAs, 5277 lincRNAs, 7625 pseudogenes, and 2730 additional lncRNAs. As a first step towards inferring the functions of the identified lncRNAs in developing B-cells, we analysed their co-expression with well-characterized protein-coding genes, a method known as guilt by association. By using weighted gene co-expression network analysis, we identified 272 lincRNAs, 471 antisense RNAs, 376 pseudogene RNAs, and 64 lncRNAs within seven sub-networks associated with distinct stages of B-cell development, such as early B-cell development, B-cell proliferation, affinity maturation of antibody, and terminal differentiation. These data provide an important resource for future studies on the functions of lncRNAs in development of the adaptive immune response, and the pathogenesis of B-cell malignancies that originate from distinct B-cell subpopulations.
Long Noncoding RNA Expression during Human B-Cell Development.
Specimen part, Subject
View SamplesWe report the effect of NAFLD on liver gene expression changes that could impact tetrachloroethhylene metabolism Methods: We fed male C57Bl/6J mice a base diet (BD), high fat (HFD), or methionine/choline/folate deficient high fat diet (MCD) for 8 weeks and then treated them with vehicle or tetrachloroethylene (PERC, 300 mg/kg ig). We only report "basal" differences herein (aka vehicle-treated). Results: We report that there were diet-specific differences in xenobiotic metabolizing genes, and that these genes may be responsible for NAFLD-induced disruption in PERC metabolism Overall design: Examination of liver left lobe gene expression for 3 different diets fed to C57Bl/6J male mice
Impact of Nonalcoholic Fatty Liver Disease on Toxicokinetics of Tetrachloroethylene in Mice.
Sex, Cell line, Treatment, Subject
View SamplesOral squamous cell carcinoma (OSCC) is a lethal disease and early death usually occurs as a result of local invasion and regional lymph node metastases. We used microarrays to identify down or upregulated genes in OSCCs compared with non-malignant controls.
Upregulation of Eps8 in oral squamous cell carcinoma promotes cell migration and invasion through integrin-dependent Rac1 activation.
Disease, Disease stage, Cell line
View Samples