The circadian clock in mammalian cells is cell-autonomously generated during the cellular differentiation process, but the underlying mechanisms are not understood. Here we show that perturbation of transcriptional program by constitutive expression of c-Myc and Dnmt1 ablation disrupts the differentiation-coupled emergence of the clock from mouse embryonic stem cells (ESCs). Using these model ESCs, 484 genes are identified by global gene expression analysis as correlating factors with differentiation-coupled circadian clock development. Among them, we find the misregulation of Kpna2 (Importin-alpha2) during the differentiation of the c-Myc over-expressed and Dnmt1-/- ESCs, in which sustaining cytoplasmic accumulation of PER proteins is observed. Moreover, constitutive expression of Kpna2 during the differentiation culture of ESCs significantly impairs clock development and KPNA2 facilitates cytoplasmic localization of PER1/2. These results suggest that the programmed gene expression network regulates the differentiation-coupled circadian clock development in mammalian cells, at least in part via post-transcriptional regulation of clock proteins. Overall design: Examination of whole transcriptome in ES cells and in vitro differentiated cells.
Transcriptional program of Kpna2/Importin-α2 regulates cellular differentiation-coupled circadian clock development in mammalian cells.
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View SamplesGene expression was studied in whole kidneys in a 2 x 2 design. SBH/y were contrasted with SBN/y under basal conditions and after salt loading. Thus, four groups were studied altogether. Five rats were used in each group. Altogether, 20 animals were used, and each animal was studied separately. Gene expression was done in kidney. Differential gene expression was measured 4 weeks after initiation of salt loading. At that time point hypertension invariably evolves fully in SBH/y but not in SBN/y.<br></br><br></br>Affymetrix CHP files are available on request from arrayexpress@ebi.ac.uk
Identification of hypertension-related genes through an integrated genomic-transcriptomic approach.
Sex, Age, Specimen part, Cell line, Subject, Compound
View SamplesCircadian clock oscillation emerges in mouse embryo in the later developmental stages. Although circadian clock development is closely correlated with cellular differentiation, the mechanisms of its emergence during mammalian development are not well understood. Here, we demonstrate an essential role of the post-transcriptional regulation of Clock subsequent to the cellular differentiation for the emergence of robust circadian clock oscillation in mouse fetal hearts and mESCs (mouse embryonic stem cells). In mouse fetal hearts, no apparent oscillation of cell-autonomous molecular clock was detectable in around embryonic day (E) 10 whereas robust oscillation was clearly visible in E18 heart. Temporal RNA-seq analysis using mouse fetal hearts reveals much fewer rhythmic genes in E10-12 hearts (63, no clock genes) than E17-19 (483 genes), indicating the lack of functional circadian clocks in E10 mouse fetal hearts. In both mESCs and E10 embryos, CLOCK protein was absent despite the expression of Clock mRNA, which we showed was at least partially due to miRNA-mediated translational suppression of CLOCK. The CLOCK protein is required for the robust molecular oscillation in differentiated cells, and the post-transcriptional regulation of Clock plays a key role in setting the timing for the emergence of the circadian clock oscillation during mammalian development.
Involvement of posttranscriptional regulation of <i>Clock</i> in the emergence of circadian clock oscillation during mouse development.
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View SamplesThis study was designed to investigate gene expression in kidneys of adult female Sabra rats (SBH/y and SBN/y rat strains) with two indwelling kidneys or after uni-ninephrectomy, seeking those genes that are differentially expressed between the two strains, and between animals with one or two kidneys. SBH/y after uninephrectomy develop proteinuria to a much greater extent than SBN/y. The study was performed as part of an overall effort to detect the genes that are associated with the pathophysiology of proteinuria.
Geno-transcriptomic dissection of proteinuria in the uninephrectomized rat uncovers a molecular complexity with sexual dimorphism.
No sample metadata fields
View SamplesTumors cause the induction or repression of many genes associated with inflammation. To investigate the up and down regulation of genes associated with immune stimulation or immune tolerance RNA was isolated from dendritic cells from normal or tumor bearing prostate for microarray analysis.
FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer.
Sex, Specimen part
View SamplesTumors cause the induction or repression of many genes associated with inflammation. To investigate the up and down regulation of genes associated with immune stimulation or immune tolerance RNA was isolated from dendritic cells from normal or tumor bearing prostate for microarray analysis.
FOXO3 programs tumor-associated DCs to become tolerogenic in human and murine prostate cancer.
Sex, Specimen part
View SamplesLoss of the interactions between lymphotoxin and its receptor was associated with MZM apoptotic cell clearance defects in BXD2 mice whereas loss of IFNAR in BXD2 mice normalized the function of MZMs. The analysis also intended to use MZMs isolated from BXD2-Ifnar-/- mice and BXD2 mice treated with sLTbR-Fc to identify the common pathways regulating the MZM function in these mice.
Interferon-induced mechanosensing defects impede apoptotic cell clearance in lupus.
Specimen part
View SamplesB cells are indispensable for humoral immunity, as they ultimately give rise to antibody-secreting plasma cells. During T cell-dependent antibody responses, naive B cells form germinal centers (GCs), a distinct histologic structure found in secondary lymphoid organs. Naive B cells become activated upon interaction with T cells and antigen presenting cells, and begin to rapidly proliferate and form the characteristic GC structure.
The LRF transcription factor regulates mature B cell development and the germinal center response in mice.
Age, Specimen part
View SamplesExpression data from mice exposed to intermittent hypoxia and mice reared for 12 months. We used microarrays to analyze the transcriptome of hippocampus from mice exposed to intermittent hypoxia or aged mice.
Treatment of intermittent hypoxia increases phosphorylated tau in the hippocampus via biological processes common to aging.
Specimen part, Treatment
View SamplesIdentification of the difference in responsiveness to interleukin-1alpha between M1 and M2 macrophage phenotypes.
Perivascular leukocyte clusters are essential for efficient activation of effector T cells in the skin.
Specimen part, Treatment
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