A large amount of epidemiologic data supports a role for chronic inflammation in epithelial carcinogenesis. In the lung, several studies have found that smokers with chronic obstructive pulmonary disease (COPD), an inflammatory disease of the airways and alveoli, have an increased risk of lung cancer (1.3 to 4.9 fold) compared to smokers without COPD. We have also shown that COPD-like airway inflammation induced by an aerosolized lysate of non-typeable Hemophilus influenzae (NTHi) promotes lung cancer in a Clara cell-targeted K-ras mutant mouse model (CC-LR) of lung cancer. In contrast, existing epidemiologic data suggest that allergic inflammation of the airways may be protective against lung cancer. We tested this association in a mouse model of allergic airway inflammation. CC-LR mice were sensitized to ovalbumin by intraperitoneal injection weekly for two weeks, then challenged for 30 min to an aerosol of ovalbumin in 0.9% saline weekly for eight weeks. This resulted in eosinophilic lung inflammation associated with increased levels of T helper 2 (Th2) cytokines and mucous metaplasia of airway epithelium, similar to what is seen in asthma patients. However, consistent with epidemiologic data, this type of inflammation did not result in any significant differences in lung surface tumor number (22 3 in OVA exposed vs 26 6 in control mice). We conclude that asthma-like (Th2) inflammation does not promote lung carcinogenesis in a Ras-initiated background, and demonstrate a clear specificity for the nature of inflammation in lung cancer promotion. These findings will assist in determination of the essential cells and signaling events in lung cancer promotion by inflammation.
Interleukin 6, but not T helper 2 cytokines, promotes lung carcinogenesis.
Specimen part, Treatment
View SamplesWe identify regulatory mechanisms that influence inflammation and metabolism during metabolic disease development. In addition to the other data represented in our paper, we performed RNA-seq to demonstrate a role for miR-146a, an anti-inflammatory miRNA, in regulating both inflammation and cellular metabolism during obesity. Overall design: Each sample represents pooled cells from three mice of the same genotype and treatment group. Samples were pooled before FACS to ensure sufficient cell numbers for sorting and RNA collection. WT or miR-146a-/- mice were treated with either high fat diet or normal chow diet for 14 weeks starting from 6 weeks of age. Mice were sacrificed and live, singlet CD45+ CD11b+ F4/80+ cells were sorted from the stromal vascular fraction of adipose tissue using FACS Aria. RNA was collected from the sorted cells via Qiazol/RNeasy Kit (Qiagen) and library preparation used Illumina TruSeq Stranded RNA Kit with Ribo-Zero Gold. RNA-seq was performed using Illumina HiSeq 50 cycle single-read sequencing version 4. Sequence alignment was performed through the University of Utah Bioinformatics Core Facility.
Anti-inflammatory microRNA-146a protects mice from diet-induced metabolic disease.
Specimen part, Subject
View SamplesSelenium, one of a class of selenocysteine-containing proteins (selenoproteins), is an essential micronutrient known for its cancer prevention properties. Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LCMS/ MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels. Overall design: 4 WT zebrafish samples and 4 SepH mutant samples
Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis.
Subject
View SamplesWe sequenced mRNA from zebrafish wild-type embryos, gata5 morphants, gata6 morphants, and gata5/6 morphants at bud and 6-somite developmental stages to identify genes co-operatively regulated by gata5 and gata6 during cardiomyocyte progenitor specification. Overall design: Samples were collected in duplicate, with 40 embryos per sample. Single 36-base pair reads were sequenced on the Illumina Genome Analyzer IIx
Tmem88a mediates GATA-dependent specification of cardiomyocyte progenitors by restricting WNT signaling.
No sample metadata fields
View SamplesIn this study we have examined the effect of sub-cytotoxic exposure to aristolochic acids (1.65M) at 6h, 24h and 72h on the whole-genome expression profile in a rat proximal renal tubule cell line (NRK-52E).
Aristolochic acids - Induced transcriptomic responses in rat renal proximal tubule cells in vitro.
Cell line, Time
View SamplesGene expression was examined in testis and brain tissue between two species (Xenopus laevis and Xenopus borealis) and their hybrid.
Single-species microarrays and comparative transcriptomics.
Age
View SamplesWe have sequenced the polysome-associated translating mRNAs from stage-matched wild-type and eif3ha morphant embryos at ~24 hpf stage to identify transcripts translationally regulated by eIF3ha. As a control, we have also sequenced total mRNAs from the stage-matched wild-type and eif3ha morphants as well at ~ 24 hpf. Overall design: Polysome-associated mRNAs were isolated from 300 zebrafish embryos. Total RNA was isolated from 50 zebrafish embryos. Single 36-base pair reads were sequenced on the Illumina Genome Analyzer Iix.
Translation initiation factor eIF3h targets specific transcripts to polysomes during embryogenesis.
No sample metadata fields
View SamplesWIN 18,446/RA treatment of neonatal mice was used to synchronize the initial wave of spermatogenesis and identify novel messages expressed within either germ or Sertoli cells as spermatogonia enter meiosis.
Riding the spermatogenic wave: profiling gene expression within neonatal germ and sertoli cells during a synchronized initial wave of spermatogenesis in mice.
Specimen part
View SamplesThe Gata4 transcription factor is essential for normal heart development, but the molecular basis for its function remain poorly understood. We profiled at the whole genome level transcript changes in cardiomyocytes when Gata4 is depleted from zebrafish embryos. Our objective was to elucidate the cardiomyocyte-specific molecular program functioning downstream of Gata4 in order to better understand the role of Gata4 in cardiac morphogenesis. Overall design: Six samples in total are deposited. Three replicate control samples and three replicate Gata4 morphant samples were analyzed.
Small heat shock proteins Hspb7 and Hspb12 regulate early steps of cardiac morphogenesis.
No sample metadata fields
View SamplesDistinctions between craniofacial and axial muscles exist from the onset of development and throughout adulthood. The masticatory muscles are a specialized group of craniofacial muscles that retain embryonic fiber properties throughout adulthood, suggesting that the developmental origin of these muscles may govern a pattern of expression that differs from limb muscles. To determine the extent of these differences, expression profiling of total RNA isolated from the masseter and tibialis anterior (TA) muscles of adult female mice was performed, which identified transcriptional changes in unanticipated functional classes of genes in addition to those associated with fiber type. In particular, the masseters displayed a reduction of transcripts associated with load-sensing and anabolic processes, and heightened expression of genes associated with stress. Consistent with these observations were a significantly smaller fiber cross-sectional area in masseters, significantly elevated load-sensing signaling (phosphorylated Focal Adhesion Kinase (FAK)), and increased apoptotic index in masseters compared to TA muscles. Based on these results, we hypothesize that masticatory muscles may sense and respond to load differently than limb muscles, where the drive for anabolic processes is reduced, and cell stress mediated processes are enhanced. These results establish a novel classification for the masseter muscle in the spectrum of skeletal muscle allotypes, and may provide insight into the molecular basis for specific muscle-related pathologies associated with masticatory muscles.
Expression profiling reveals heightened apoptosis and supports fiber size economy in the murine muscles of mastication.
No sample metadata fields
View Samples