Male and female CD-1 mice were administered dietary Phenobarbital for 2 or 7 days. In-life, enzyme activity, cell proliferation, genomic analysis, and Bench-mark dose modeling was carried out.
Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway.
Specimen part
View SamplesDiesel exhaust (DE) has been shown to enhance allergic sensitization in animals following high dose instillation or chronic inhalation exposure scenarios. The purpose of this study was to determine if short term exposures to diluted DE enhance allergic immune responses to antigen, and identify possible mechanisms using microarray technology. BALB/c mice were exposed to filtered air or diluted DE to yield particle concentrations of 500 or 2000 g/m3 4 hr/day on days 0-4. Mice were sensitized intranasally with ovalbumin (OVA) antigen or saline on days 0-2, and 18 and all were challenged with OVA on day 28. Mice were necropsied either 4 hrs after the last DE exposure on day 4, or 18, 48, and 96 hrs after challenge. Immunological endpoints included OVA-specific serum IgE, biochemical and cellular profiles of bronchoalveolar lavage (BAL), and cytokine production in the BAL. OVA-sensitized mice exposed to both concentrations of DE had increased eosinophils, neutrophils, lymphocytes, and IL-6 post-challenge compared to OVA control, while DE/saline exposure yielded increases in neutrophils at the high dose only. Microarray analysis demonstrated distinct gene expression profiles for the high dose DE/OVA and DE/saline groups. DE/OVA induced pathways involved in oxidative stress and metabolism while DE in the absence of allergen sensitization modulated cell cycle control, growth and differentiation, G-proteins, and cell adhesion pathways. This study shows for the first time early changes in gene expression induced by the combination of diesel exhaust inhalation and antigen sensitization, which resulted in stronger development of an allergic asthma phenotype.
Increased transcription of immune and metabolic pathways in naive and allergic mice exposed to diesel exhaust.
No sample metadata fields
View SamplesNote: non-normalized values and associated raw data cannot be located by the submitter
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View SamplesUse of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-seq offers a novel way to address this problem. In this study we evaluated transcriptomic dose responses using RNA-seq in paired FFPE and frozen (FROZ) samples from two archival studies in mice, one recent (<2 years old) and the other older (>20 years old). Experimental treatments included di(2-ethylhexyl)phthalate (DEHP) and dichloroacetic acid (DCA) for the <2 and >20 year-old studies, respectively. Total RNA was ribodepleted and sequenced using the Illumina HiSeq platform. In the recent study, FFPE samples showed high concordance in total reads (98% vs FROZ), fold-change values of differentially expressed genes (DEGs) (R2 = 0.99), highly enriched target pathways (90% overlap with FROZ), and benchmark dose estimates for preselected target genes (-2% overall vs FROZ). In contrast, RNA-seq data from older FFPE samples had lower total reads (70% vs FROZ) and poor concordance in global DEGs and pathways. Despite a 99% loss of counts, dose responses were still evident for target genes in FFPE samples and positively correlated with paired FROZ samples. These findings highlight potential variability in the quality of RNA-seq data from FFPE samples. More recent FFPE samples were highly similar to FROZ samples in sequencing quality metrics, DEG profiles, and dose-response parameters, while further methods development is needed for older or lower-quality FFPE samples. This work should help broaden the use of archival resources in both chemical safety and translational science. Overall design: Trancriptomic profiles obtained using from paired frozen (FROZ) and formalin-fixed paraffin-embedded (FFPE) liver samples collected in 2013 for the DEHP study (n=16 FROZ, n=16 FFPE, with four dose groups at 0, 1500, 3000, and 6000 ppm DEHP, n=4 per dose group) and 1994 for the DCA study (n=24 FROZ, n=24 FFPE, with four dose groups at 0, 1.0, 2.0, and 3.5 g/L DCA, n=6 per dose group) using Illumina HiSeq platform.
Editor's Highlight: Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-Fixed Paraffin-Embedded Samples.
Sex, Age, Specimen part, Cell line, Treatment, Subject
View SamplesThe aim of this study is to characterize transcriptional changes induced by maternal diet in several adult tissues and to test whether differences in DNA methylation or microRNA expression could explain these changes.
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View SamplesThe aim of this study is to characterize transcriptional changes induced by maternal diet in several adult tissues and to test whether differences in DNA methylation or microRNA expression could explain these changes.
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View SamplesThe aim of this study is to characterize transcriptional changes induced by maternal diet in several adult tissues and to test whether differences in DNA methylation or microRNA expression could explain these changes.
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View SamplesThe aim of this study is to characterize transcriptional changes induced by maternal diet in several adult tissues and to test whether differences in DNA methylation or microRNA expression could explain these changes.
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View SamplesThe aim of this study is to characterize transcriptional changes induced by maternal diet in several adult tissues and to test whether differences in DNA methylation or microRNA expression could explain these changes.
Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of tissue-specific transcriptional markers of caloric restriction in the mouse and their use to evaluate caloric restriction mimetics.
Sex, Specimen part
View Samples