Cultured epidermal keratinocytes treated with OsM 1, 4, 24 & 48hrs, and Skinethic epidermal substitutes treated 1, 4, 24, 48h & 7days, each with untreated control
Transcriptional responses of human epidermal keratinocytes to Oncostatin-M.
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Sexual selection involves mate preference behavior and is a critical determinant for natural selection and evolutionary biology. Previously an environmental compound (fungicide vinclozolin) was found to promote epigenetic transgenerational inheritance of modified mate selection characteristics in all progeny for three generations after exposure of a gestating female. The current study investigated gene networks involved in various regions of the brain that correlated with the mate preference behavior altered in F3-Vinclozolin lineage animals. Statistically significant correlations of differentially expressed gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified critical gene networks involved in mate preference behavior and demonstrated the ability of environmental factors to promote epigenetic transgenerational inheritance of this altered evolutionary biology determinant. Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology.
Gene bionetworks involved in the epigenetic transgenerational inheritance of altered mate preference: environmental epigenetics and evolutionary biology.
Sex, Age, Specimen partView Samples
Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.
Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.
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UMR106-01 osteoblastic cells are a model for studying bone mineralization. We have shown that mineralization is temporally synchronized within cultures grown under defined conditions . Cells are plated at time zero and differentiate into osteoblastic phenotype by 64 h later. If an exogenous phosphate source is added to the cultures, the cells form and deposit hydroxyapatite mineral within distinct extracellular supramolecular lipid protein complexes termed biomineralization foci (BMF) starting 12 h later. Mineralization is largely complete by 24 h later (88 h after plating). We have also shown that AEBSF, covalent serine protease inhibitor, blocks mineralization within BMF and inhibits the fragmentation of several proteins related to biomineralization. The present experiment was designed to test whether AEBSF treatment for 12 h has an effect on transcription by UMR106-01 osteoblastic cells. AEBSF is known to inactivate several serine proteases including SKI-1 (site 1, subtilisin kexin protease-1).SKI-1 functions intracellularly to activate transmembrane bound transcription factor precursors releasing the transcriptionally active N-terminal portions to imported into the nucleus. Thus, if AEBSF blocks transcription of mineralization related genes, it would support a role for SKI-1 in gene regulation in mineralizing UMR106-01 osteoblastic cells.
Inhibition of proprotein convertase SKI-1 blocks transcription of key extracellular matrix genes regulating osteoblastic mineralization.
Cell lineView Samples
In this experiment, total RNA was extracted from asynchronous population of L1210 cells and hybridized to Affymetrix 430A 2.0 arrays in order to obtain an expression profile of these cells. We have previously mapped the replication timing of the entire mouse genome in this cell line, using mouse CGH arrays (see E-MEXP-1022). We wanted to validate in our system the known correlation between early replication and expression and to analyze its extent. To this end, we have measured the expression in the same cell line (L1210 cells). Two biological replicates were hybridized to 2 identical microarrays. Expression levels were highly similar between the 2 replicates (r=0.98).
Global organization of replication time zones of the mouse genome.
Cell line, SubjectView Samples
Use of expression data to analyse ovarian cancer often yields long lists of genes that do not agree across various studies. Copy number however is more stable and can reliable predict important regions of change. Using matched copy number and expressiion data helps accurately identify novel drivers of ovarian cancer.
Identification of candidate growth promoting genes in ovarian cancer through integrated copy number and expression analysis.
Age, Disease stageView Samples
The objective of this experiment was to determine global gene expression change in triple negative cell line upon knockdown of TGFBR3. Genotype specific differences in expression profiles have been evaluated using human HuGene1.0-ST affymetrix array. RNA was extracted from SUM159 controls and SUM159 TGFBR3KD cells cultured in 3-dimensional in vitro system.
Transforming growth factor beta receptor type III is a tumor promoter in mesenchymal-stem like triple negative breast cancer.
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Mycobacterium bovis is an intracellular pathogen that causes tuberculosis in cattle. Following infection, the pathogen resides and persists inside host macrophages by subverting host immune responses via a diverse range of mechanisms. Here, a high-density bovine microarray platform was used to examine the bovine monocyte-derived macrophage transcriptome response to M. bovis infection relative to infection with the attenuated vaccine strain, M. bovis Bacille CalmetteGurin. Differentially expressed genes were identified (adjusted P-value 0.01) and interaction networks generated across an infection time course of 2, 6 and 24 h. The largest number of biological interactions was observed in the 24 h network, which exhibited small-worldscale-free network properties. The 24 h network featured a small number of key hub and bottleneck gene nodes, including IKBKE, MYC, NFKB1 and EGR1 that differentiated the macrophage response to virulent and attenuated M. bovis strains, possibly via the modulation of host cell death mechanisms. These hub and bottleneck genes represent possible targets for immunomodulation of host macrophages by virulent mycobacterial species that enable their survival within a hostile environment.
Key Hub and Bottleneck Genes Differentiate the Macrophage Response to Virulent and Attenuated Mycobacterium bovis.
Sex, Age, Specimen part, Treatment, TimeView Samples
To define the molecular regulators of metastasis of triple-negative breast cancer, we conducted a rigorous characterization of four isogenic populations of MDA-MB-231 human triple-negative breast cancer cells that display a range of intrinsic spontaneous metastatic capacities in immuno-deficient mice, from non-metastatic to highly metastatic to lung, liver, spleen and spine. PAT-Seq gene expression profiling of primary tumor cells identified the fibroblast growth factor homologous factor, FGF13, as a candidate metastatic virulence gene highly upregulated in aggressively metastatic MDA-MB-231HM tumors. Overall design: Gene expression analysis from PAT-Seq of 4 increasingly metastatic breast cancer xenograft tumours
Functional and genomic characterisation of a xenograft model system for the study of metastasis in triple-negative breast cancer.
Specimen part, SubjectView Samples
Background: Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix GeneChip Bovine Genome Array with features representing more than 23,000 gene transcripts and over 19,000 gene probe sets.
Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes.
Sex, Specimen partView Samples