This SuperSeries is composed of the SubSeries listed below.
Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells.
Sex, Age, Specimen part
View SamplesMammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life.
Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells.
Sex, Specimen part
View SamplesMammary gland development and luminal differentiation occur largely postnatally during puberty and pregnancy. To explore the role of DNA methylation in luminal cell differentiation and pregnancy-induced changes, we determined the genome-wide DNA methylation and gene expression profiles of mammary epithelial stem, luminal progenitor, and mature luminal cells at different reproductive stages. We found that pregnancy had the most significant effects on stem cells, inducing a distinct epigenetic state that remained stable through life. Integrated analysis of gene expression, DNA methylation, and histone modification profiles revealed cell type and reproductive stage-specific changes in molecular signatures. We also identified p27 and TGF signaling as key regulators of luminal progenitor cell proliferation based on their expression patterns and by the use of explant cultures. Our results suggest relatively minor changes in DNA methylation during luminal cell differentiation as compared to the significant effects of pregnancy on mammary epithelial stem cells.
Age- and pregnancy-associated DNA methylation changes in mammary epithelial cells.
Sex, Specimen part
View SamplesThe sexually dimorphic expression of genes across 26 somatic rat tissues was using Affymetrix RAE-230 genechips. We considered probesets to be sexually dimorphically expressed (SDE) if they were measurably expressed above background in at least one sex, there was at least a two-fold difference in expression (dimorphism) between the sexes, and the differences were statistically significant after correcting for false discovery. 14.5% of expressed probesets were SDE in at least one tissue, with higher expression nearly twice as prevalent in males compared to females. Most were SDE in a single tissue. Surprisingly, nearly half of the probesets that were (SDE) in multiple tissues were oppositely sex biased in different tissues, and most SDE probesets were also expressed without sex bias in other tissues. Two genes were widely SDE: Xist (female-only) and Eif2s3y (male-only). The frequency of SDE probesets varied widely between tissues, and was highest in the duodenum (6.2%), whilst less than 0.05% in over half of the surveyed tissues. The occurrence of SDE probesets was not strongly correlated between tissues. Within individual tissues, however, relational networks of SDE genes were identified. In the liver, networks relating to differential metabolism between the sexes were seen. The estrogen receptor was implicated in differential gene expression in the duodenum. To conclude, sexually dimorphic gene expression is common, but highly tissue-dependent. Sexually dimorphic gene expression may provide insights into mechanisms underlying phenotypic sex differences.
The incidence of sexually dimorphic gene expression varies greatly between tissues in the rat.
Sex, Specimen part
View SamplesMany heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the of toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays.
Exposure to nickel, chromium, or cadmium causes distinct changes in the gene expression patterns of a rat liver derived cell line.
No sample metadata fields
View SamplesThe principal toxicity of acute organophosphate (OP) pesticides poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethalityparticularly through the inhibition of AChEstudies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms.
Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery.
No sample metadata fields
View SamplesThe goal of this study is to identify, in the head of adult flies, mRNA species whose expresson level are altered by overexpression of the Drosophila RNA-binding protein LARK in CNS neurons.
The LARK RNA-binding protein selectively regulates the circadian eclosion rhythm by controlling E74 protein expression.
No sample metadata fields
View SamplesThe Wnt signaling pathway plays a fundamental role during the development of metazoans, where it functions in the regulation of diverse processes including cell fate specification, cell migration, and stem cell renewal. Activation of the beta-catenin dependent or canonical Wnt signaling pathway upregulates expression of Wnt target genes to mediate an appropriate cellular response. In the nematode C. elegans, a Wnt signaling pathway similar to the canonical pathway regulates several processes during larval development, however few target genes of this pathway have been identified. To address this deficit, we conditionally activated Wnt signaling in living animals during a defined stage of larval life by expressing a dominant, activated beta-catenin protein, then used microarray analysis to identify genes showing altered expression compared to control animals. In this way we identified 166 differentially expressed genes, of which 104 were upregulated. A subset of the upregulated genes were validated by qPCR and showed altered expression in Wnt pathway mutants with decreased or increased Wnt signaling; we consider these genes to be candidate Wnt pathway targets in the C. elegans hermaphrodite larva. Amongst these was a group of 6 genes, including the cuticular collagen genes, bli-1 col-38, col-49 and col-71, that show a peak of expression in the mid L4 stage during normal development. The L4 expression of these genes suggests they may be expressed for use in the adult cuticle, and consistent with this, reduction of function for several of the genes leads to phenotypes suggestive of defects in cuticle function or integrity. Therefore this work has identified a large number of putative Wnt pathway target genes during larval life, including a small subset of Wnt-regulated collagen genes that may function in synthesis of the adult cuticle.
Use of an activated beta-catenin to identify Wnt pathway target genes in caenorhabditis elegans, including a subset of collagen genes expressed in late larval development.
No sample metadata fields
View SamplesCircadian behaviors are regulated by intrinsic biological clocks consisting of central molecular oscillators and output pathways. Despite significant progress in elucidating the central timekeeping mechanisms, the molecular pathways coupling the circadian pacemaker to overt rhythmic behavior and physiology remain elusive. The Drosophila LARK RNA-binding protein is a candidate for such a coupling factor. Previous research indicates that LARK functions downstream of the clock to mediate behavioral outputs. To better understand the roles of LARK in the Drosophila circadian system, we sought to identify RNA molecules associated with LARK in vivo, using a novel strategy that involves capturing the RNA ligands by immunoprecipitation, visualizing the captured RNAs using whole gene microarrays, and identifying functionally relevant targets through genetic screens.
The LARK RNA-binding protein selectively regulates the circadian eclosion rhythm by controlling E74 protein expression.
No sample metadata fields
View SamplesIntrinsic variations in the development of lung injury among patients undergoing radiotherapy for tumors in the thoracic region suggest there are one or more genes that influence the development and severity of radiation pneumonitis and/or fibrosis.
Pathophysiological mechanisms underlying phenotypic differences in pulmonary radioresponse.
No sample metadata fields
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