In the past decade, several transcription factors critical for pancreas development have been identified. Despite this success, many of the cell surface and extracellular factors necessary for proper islet morphogenesis and function remain uncharacterized. Previous studies have shown that transgenic over-expression of the transcription factor HNF6 specifically in the pancreatic endocrine cell lineage resulted in the disruption of islet morphogenesis, including dysfunctional endocrine cell sorting, increased islet size, and failure of islets to migrate away from the ductal epithelium. We exploited the dysmorphic islets in pdx1PBHnf6 animals as a tool to identify factors important for islet morphogenesis. Genome-wide microarray analysis was used to identify differences in the gene expression profiles of late gestation and early postnatal pancreas tissue from wild type and pdx1PBHnf6 animals. We report the identification of genes with an altered expression in HNF6 Tg animals and highlight factors with potential importance in islet morphogenesis.
Gene expression profiling of a mouse model of pancreatic islet dysmorphogenesis.
Specimen part
View SamplesWe hypothesize that germline variation influences susceptibility to aggressive prostate tumor
GNL3 and SKA3 are novel prostate cancer metastasis susceptibility genes.
Specimen part
View SamplesWe hypothesize that germline variation influences susceptibility to aggressive prostate tumor
A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.
Sex, Specimen part
View SamplesActivators of innate immunity may have potential to combat a broad range of infectious agents. We report that treatment with bacterial flagellin prevented rotavirus (RV) infection in mice and cured chronically RV-infected mice. Protection was independent of adaptive immunity and interferon (IFN, type I and II) and required flagellin receptors Toll-like receptor 5 (TLR5) and NOD-like receptor C4 (NLRC4). Flagellin-induced activation of TLR5 on dendritic cells elicited production of the cytokine interleukin (IL)-22, which induced a protective gene expression program in intestinal epithelial cells. Flagellin also induced NLRC4-dependent production of IL-18 and immediate elimination of RV-infected cells. Administration of IL-22 and IL-18 to mice fully recapitulated the capacity of flagellin to prevent or eliminate RV infection, and thus holds promise as a broad-spectrum antiviral agent. Overall design: Total mRNA from intestinal epithelial cells of Rag1-/- mice treated with PBS, IL-18, IL-22 or IL-22/IL-18 was assayed for RNA sequencing.
Viral infection. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18.
No sample metadata fields
View SamplesThese samples are being analyzed by the Duke-UNC-Texas-EBI ENCODE consortium. Expression from these cell types will compared to three whole genome open chromatin methodologies: DNaseI hypersensitivity (DNase-seq), Formaldehyde-Assisted Isolation of Regulatory elements (FAIRE-seq), and Chromatin Immunoprecipitation (ChIP-seq) .
Heritable individual-specific and allele-specific chromatin signatures in humans.
Specimen part
View SamplesRNA-seq analysis of 195 randomly selected (TRAMP x J:DO) F1 prostates that had been harvested at experimental termination (210 days or humane endpoints) was performed to identify metastasis associated transcriptomic changes Overall design: Total RNA expression profile of TRAMP x DO F1 prostate tumors
Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer.
Cell line
View SamplesWe identified CENPU as prostate cancer metastases genes by analyzing QTL, transcript profiles and SNP associations with aggressive disease phenotypic traits in transgenic mice and human cohorts
Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer.
Cell line
View SamplesWe identified RWDD4 as prostate cancer metastases genes by analyzing QTL, transcript profiles and SNP associations with aggressive disease phenotypic traits in transgenic mice and human cohorts
Mapping Complex Traits in a Diversity Outbred F1 Mouse Population Identifies Germline Modifiers of Metastasis in Human Prostate Cancer.
Cell line
View SamplesCharacterization of bacterial behavior in the microgravity environment of spaceflight is of importance towards risk assessment and prevention of infectious disease during long-term missions. Further, this research field unveils new insights into connections between low fluid-shear regions encountered by pathogens during their natural infection process in vivo, and bacterial virulence. This study is the first to characterize the global transcriptomic and proteomic response of an opportunistic pathogen that is actually found in the space habitat, Pseudomonas aeruginosa. Overall, P. aeruginosa responded to spaceflight conditions through differential regulation of 167 genes and 28 proteins, with Hfq identified as a global transcriptional regulator in the response to this environment. Since Hfq was also induced in spaceflight-grown Salmonella typhimurium, Hfq represents the first spaceflight-induced regulator across the bacterial species border. The major P. aeruginosa virulence-related genes induced in spaceflight conditions were the lecA and lecB lectins and the rhamnosyltransferase (rhlA), involved in the production of rhamnolipids. The transcriptional response of spaceflight-grown P. aeruginosa was compared with our previous data of this organism grown in microgravity-analogue conditions using the rotating wall vessel (RWV) bioreactor technology. Interesting similarities were observed, among others with regard to Hfq regulation and oxygen utilization. While LSMMG-grown P. aeruginosa mainly induced genes involved in microaerophilic metabolism, P. aeruginosa cultured in spaceflight adopted an anaerobic mode of growth, in which denitrification was presumably most prominent. Differences in hardware between spaceflight and LSMMG experiments, in combination with more pronounced low fluid shear and mixing in spaceflight when compared to LSMMG conditions, were hypothesized to be at the origin of these observations. Collectively, our data suggest that spaceflight conditions could induce the transition of P. aeruginosa from an opportunistic organism to potential pathogen, results that are of importance for infectious disease risk assessment and prevention, both during spaceflight missions and in the clinic.
Transcriptional and proteomic responses of Pseudomonas aeruginosa PAO1 to spaceflight conditions involve Hfq regulation and reveal a role for oxygen.
No sample metadata fields
View Samples