Rorb is essential for rod photoreceptor development in the mouse retina. Using Affymetrix mouse GeneChips, we have generated expression profiles of the +/+, Rorb-/- , +/+;CrxpNrl and Rorb-/-;CrxpNrl retina at P14 and P28.
Retinoid-related orphan nuclear receptor RORbeta is an early-acting factor in rod photoreceptor development.
Specimen part
View SamplesZebrafish embryos are sensitive to chemical substance and often used as a in vivo model for enviromental toxicology research.
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View SamplesSelective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressant drugs in pregnant women. Given that SSRIs can cross the placental and blood-brain barriers, these drugs potentially affect serotonergic neurotransmission and neurodevelopment in the fetus. Although no gross SSRI-related teratogenic effect has been reported, infants born following prenatal exposure to SSRIs have a higher risk for various behavioral abnormalities. Therefore, we examined the effects of prenatal fluoxetine, the most commonly prescribed SSRI, on social and cognitive behavior in mice. Intriguingly, chronic in utero fluoxetine treatment impaired working memory and social novelty recognition in adult males with augmented spontaneous inhibitory synaptic transmission onto the layer 5 pyramidal neurons in the medial prefrontal cortex (mPFC). Moreover, fast-spiking interneurons in the layer 5 mPFC exhibited enhanced basal intrinsic excitability, augmented serotonin-induced neuronal excitability, and increased inhibitory synaptic transmission onto the layer 5 pyramidal neurons due to augmented 5-HT2A receptor (5-HT2AR) signaling. More importantly, the observed behavioral deficits of in utero fluoxetine-treated mice could be reversed by acute systemic application of 5-HT2AR antagonist. Taken together, our findings support the notion that alterations in serotonin-mediated inhibitory neuronal modulation result in reduced cortical network activities and cognitive impairment following prenatal exposure to SSRIs.
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Sex, Specimen part, Treatment
View SamplesSnail1 is a master epithelial-mesenchymal trisition (EMT) factor but its role in ESC maintenance is unknown.
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Specimen part
View SamplesPPARg and C/EBPa cooperate to control preadipocyte differentiation (adipogenesis). However, the factors that regulate PPARg and C/EBPa expression during adipogenesis remain largely unclear. Here we show PTIP, a protein that associates with histone H3K4 methyltransferases, regulates PPARg and C/EBPa expression in mouse embryonic fibroblasts (MEFs) and during preadipocyte differentiation. PTIP deletion in MEFs leads to marked decreases of PPARg expression and PPARg-stimulated C/EBP expression. Further, PTIP is essential for induction of PPARg and C/EBPa expression during preadipocyte differentiation. Deletion of PTIP impairs the enrichment of H3K4 trimethylation and RNA polymerase II on PPARg and C/EBPa promoters. Accordingly, PTIP-/- MEFs and preadipocytes all show striking defects in adipogenesis. Furthermore, rescue of the adipogenesis defect in PTIP-/- MEFs requires co-expression of PPARg and C/EBPa. Finally, deletion of PTIP in brown adipose tissue significantly reduces tissue weight in mice. Thus, by regulating PPARg and C/EBPa expression, PTIP plays a critical role in adipogenesis.
Histone methylation regulator PTIP is required for PPARgamma and C/EBPalpha expression and adipogenesis.
Cell line
View SamplesUTX gene is localized on the X chromosome, identified as a demethylase on histone H3 lysine 27.
UTX regulates mesoderm differentiation of embryonic stem cells independent of H3K27 demethylase activity.
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View SamplesTo predict Rp58-regulated gene involved in myogenesis, RNA profiling experiments were performed, comparing RNA derived from C2C12 with or without expressing shRNA for Rp58. As a result, 271 genes were upregulated in C2C12 stably expressing shRNA-Rp58 cells compared with control C2C12 cells. As Rp58 is repressor in C2C12, we hypothesized that Rp58 regulates gene cluster which expression is downregulated in accordance with Rp58 expression and myogenesis progression. In this regard, we also characterized dynamic gene expression patterns during myogenesis by microarray at 4 different stage (GM, day 0, 2, 4) of C2C12 myogenesis assays and found that 399 genes expression is characterized as downregulation pattern during myogenesis. Importantly, this down regulation gene set and upregulated genes by shRNA for Rp58 were highly overlapped.
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View SamplesAnalysis of mouse chondrocytes lacking the microRNA-140. MicroRNAs are genomically encoded small RNAs to regulate the gene expression. miR-140 shows high expression in cartilage. Results provide insight into the molecular mechanisms underlying miR-140 function in chondrocytes.
MicroRNA-140 plays dual roles in both cartilage development and homeostasis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reprogramming factor expression initiates widespread targeted chromatin remodeling.
Specimen part
View SamplesDespite rapid progress in characterizing transcription factor-driven reprogramming of somatic cells to an induced pluripotent stem (iPS) cell state, many mechanistic questions still remain. To gain insight into the earliest events in the reprogramming process, we systematically analyzed the transcriptional and epigenetic changes that occur during early factor induction after discrete numbers of divisions. We observed rapid, genome-wide changes in the euchromatic histone modification, H3K4me2, at more than a thousand loci including large subsets of pluripotency or developmentally related gene promoters and enhancers. In contrast, patterns of the repressive H3K27me3 modification remained largely unchanged except for focused depletion specifically at positions where H3K4 methylation is gained. These chromatin regulatory events precede transcriptional changes within the corresponding loci. Our data provide evidence for an early, organized, and population-wide epigenetic response to ectopic reprogramming factors that clarify the temporal order through which somatic identity is reset during reprogramming.
No associated publication
Specimen part
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