Genomic imprinting results in the preferential expression of the paternal, or maternal allele of certain genes. We have performed a genome-wide characterization of imprinting in the mouse embryonic and adult brain using F1 hybrid mice generated from reciprocal crosses of CASTEiJ and C57BL/6J mice. We also uncovered genes associated with sex specific parental effects in the adult mouse brain. Our study identified preferential selection of the maternally inherited X chromosome in glutamatergic neurons of the female cortex. Overall design: Examination of allele specific expression in the brains of reciprocal crosses of F1 hybrid mice from CASTEiJ and C57BL/6J crosses. Processed data files (GenomicAligned, SNP_calls, TranscriptomeAligned, fRNAdbAligned) and README file linked below as supplementary files.
Sex-specific parent-of-origin allelic expression in the mouse brain.
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View SamplesThe hippocampus is part of a brain network essential for memory function. Paradoxically, the hippocampus is also the brain structure that is most sensitive to hypoxic-ischemic episodes. Here we show that the expression of genes associated with glycolysis and glutamate metabolism in astrocytes and the coverage of excitatory synapses by astrocytic processes undergo significant decreases in the CA1 field of the monkey hippocampus during postnatal development. Given the established role of astrocytes in the regulation of glutamate concentration in the synaptic cleft, our findings indicate that a developmental decrease in astrocytic processes underlies the selective vulnerability of CA1 during hypoxic-ischemic episodes in adulthood, its decreased susceptibility to febrile seizures with age, as well as contribute to the emergence of selective, adult-like memory function.
Developmental regulation of gene expression and astrocytic processes may explain selective hippocampal vulnerability.
Specimen part
View SamplesThe prostate represents a complex mix of cell types and there is a need to analyze distinct cell populations to better understand their potential interactions. This study of cell-type specific gene expression patterns will contribute to understanding of how tumor epithelial cells may be affected by adjacent interstitial stromal cells within the tumor microenvirnonment.
Analysis of gene expression in prostate cancer epithelial and interstitial stromal cells using laser capture microdissection.
Specimen part, Disease, Disease stage
View SamplesBlood genomic profiling has been applied to disorders of the blood and various organ systems including brain to elucidate disease mechanisms and identify surrogate disease markers. Since most studies have not examined specific cell types, we performed a preliminary genomic survey of major blood cell types from normal individuals using microarrays. CD4+ T cells, CD8+ T cells, CD19+ B cells, CD56+ natural killer cells, and CD14+ monocytes were negatively selected using the RosetteSep antibody cocktail, while polymorphonuclear leukocytes were separated with density gradient media.
Genomic profiles for human peripheral blood T cells, B cells, natural killer cells, monocytes, and polymorphonuclear cells: comparisons to ischemic stroke, migraine, and Tourette syndrome.
Specimen part, Disease
View SamplesPreviously published results from our double-blind, placebo-controlled parallel study with docosahexaenoic acid (DHA) supplementation (3 g/d, 90 d) to hypertriglyceridemic men (39-66yr) showed that DHA reduced several risk factors for cardiovascular disease (CVD), including the plasma concentration of inflammatory markers. To determine the effect of DHA supplementation on the global gene expression pattern, we performed Affymetrix GeneChip microarray analysis of blood cells (treated with lipopolysaccharide (LPS) or vehicle) drawn before and after the supplementation from the hyperlipidemic men who participated in the previous study. Genes that were significantly differentially regulated by the LPS treatment and DHA supplementation were identified. Differential regulation of 18 genes was then confirmed by quantitative RT-PCR. Both microarray and qRT-PCR data showed that the expression of LDL receptor (LDLR), oxidized LDL receptor (OLR1), and cathepsin L1 (CTSL) was significantly suppressed by DHA supplementation; however, LPS stimulated the expression of LDLR and CTSL but not that of OLR1. LPS up-regulated and DHA suppressed the expression of prostaglandin E synthase (PTGES), PPAR delta, and various chemokines. Enrichment with Gene Ontology categories demonstrated that the genes related to transcription factor activity, immune responses, host defense responses, inflammatory responses, and apoptosis were inversely regulated by LPS and DHA. These results provide supporting evidence for the anti-inflammatory effects of DHA supplementation, and reveal previously unrecognized genes that are regulated by DHA, and are associated with risk factors of cardiovascular diseases.
Modulation of blood cell gene expression by DHA supplementation in hypertriglyceridemic men.
Specimen part, Disease
View SamplesDetermine allele level expression in hybrid mice of different ages Overall design: RNASeq - HybridMouseDRN
Diverse Non-genetic, Allele-Specific Expression Effects Shape Genetic Architecture at the Cellular Level in the Mammalian Brain.
Sex, Specimen part, Subject
View SamplesThese data provide scientific information to understand the mechanism of action of lapatinib resistance in HER2-positive patients and to test the combination of HER2-targeted agents and GSK1363089 (foretinib) in the clinic by using an acquired lapatinib-resistant cell line.
Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL.
Specimen part, Cell line, Treatment
View SamplesEpigenetic and genetic regulations are sometimes considered as separate mechanisms that influence gene expression and phenotypes. However, there are DNA sequence variants in epigenetic regulators that could affect gene regulation. The histone demethylase, KDM4C, promotes transcriptional activation by removing the repressive histone mark, tri-methylation of lysine 9 of histone H3 (H3K9me3), from its target genes. In this study, we uncovered cis-acting DNA sequence variants in KDM4C that contribute to individual differences in its expression. Utilizing this natural variation, we performed genetic analyses in B-cells in order to identify target genes that are regulated by KDM4C.
Natural variation in the histone demethylase, KDM4C, influences expression levels of specific genes including those that affect cell growth.
Specimen part
View SamplesGene expression in blood of children with autism spectrum disorder (ASD) was studied. Transcriptional profiles were compared with age and gender matched, typically developing children from the general population (GP) or IQ matched children with mental retardation or developmental delay (MR/DD).
Gene expression changes in children with autism.
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View SamplesTo study the gene expression changes in mesenchymal stem cells from bone marrow stroma (MSCs) during in vitro expansion (from low density), passage 1 MSC were grown in culture for 15 days with medium change every 2-3 days. Samples for microarrays were taken at day 5 (early log-phase), 10 (late log-phase) and 15 (stationary phase). The data was queried for expression changes in Wnt signaling molecules and cell surface markers. Several components of the canonical Wnt signaling pathway were expressed, including Dkk-1; Wnt-5a; alpha-catenin; beta-catenin; frizzled 1, 4, 6, and 7; disheveled; glycogen synthetase kinase 3 beta; and glycogen synthetase kinase 3 alpha. In addition, the expression of over 10 cell surface transcripts decreased and an almost equal number increased during expansion. The two of the transcripts with the largest decreases coded for proteins previously shown to be linked to cell motility and tumor progression: PODXL, and alpha6-integrin (CD49f). As the cultures expanded, the largest increase was for mRNA for the cell adhesion protein VCAM-1. To study the gene expression changes in more detail, real-time RT-PCR, RT-PCR, ELISAs, FACS, and western blotting were performed for additional MSC donors. The results demonstrated dramatic changes in the transcriptome of MSCs during in vitro expansion.
The Wnt signaling inhibitor dickkopf-1 is required for reentry into the cell cycle of human adult stem cells from bone marrow.
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