Inadequate remyelination of brain white matter lesions has been associated with a failure of oligodendrocyte precursors to differentiate into mature, myelin-producing cells. In order to better understand which genes play a specific role in oligodendrocyte differentiation we performed time dependent, genome-wide gene expression studies of mouse Oli-neu cells as they differentiate into myelin basic protein-producing cells, following treatment with three different agents. Our data indicate that different inducers activate distinct pathways that ultimately converge into the differentiated state where regulated gene sets overlap maximally.
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View SamplesObjective. To identify novel monosodium urate (MSU) crystal-induced mRNAs by transcript profiling of isolated murine air pouch membranes.
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View SamplesTrophoblast stem cells (TS cells), derived from the trophectoderm (TE) of blastocysts, require transcription factors (TFs) and external signals (Fgf4, Activin/Nodal/Tgfb) for self-renewal. While many reports have focused on TF networks that regulate embryonic stem cell (ES cell) self-renewal and pluripotency, little is know about TF networks that regulate self-renewal in TS cells. To further understand transcriptional networks in TS cells we used chromatin immunopreciptiation and DNA microarray analysis (ChIP-chip) to investigate targets of TFs Ap-2g (Tcfap2c), Eomes, Ets2, and Gata3, and a chromatin remodeling factor, Brg1 (Smarca4). We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide analysis of histone H3 acetylation (AcH3). Our results describe previously unknown transcriptional networks in TS cells, including TF occupancy of genes involved in ES cell self-renewal and pluripotency, co-occupancy of multiple TFs at target genes, and transcriptional regulatory circuitry within the 5 factors. Through genome-wide mapping and global expression analysis of 5 TF target genes, our data provide a comprehensive analysis of transcriptional networks that regulate TS cell self-renewal.
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Specimen part, Time
View SamplesEpigenetic regulation of gene expression is important in maintaining self-renewal of embryonic stem (ES) cells and trophoblast stem (TS) cells. Histone deacetylases (HDACs) negatively control histone acetylation by removing covalent acetylation marks from histone tails. Because histone acetylation is a known mark for active transcription, HDACs presumably associate with inactive genes. Here, we used genome-wide chromatin immunoprecipitation to investigate targets of HDAC1 in ES cells and TS cells. Through evaluation of genes associated with acetylated histone H3 marks, and global expression analysis of Hdac1 knockout ES cells and trichostatin A treated ES cells and TS cells, we found that HDAC1 occupies mainly active genes, including important regulators of ES cell and TS cell self-renewal. By mapping HDAC1 targets on a global scale, our results describe further insight into epigenetic mechanisms of ES cell and TS cell self-renewal.
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Specimen part, Treatment
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