Circadian networks in human embryonic stem cell-derived cardiomyocytes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE97142 | GEO | 2017/05/12
SECONDARY ACCESSION(S): PRJNA381615
REPOSITORIES: GEO
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2020-03-11 | GSE131843 | GEO
Project description:Aim: Innate circadian rhythms are critical for optimal tissue-specific functions, including skeletal muscle, a major insulin-sensitive tissue responsible for glucose homeostasis. We determined whether transcriptional oscillations are associated with CpG methylation changes in skeletal muscle. Materials & methods: We performed rhythmicity analysis on the transcriptome and CpG methylome of circadian synchronized myotubes. Results: We identified several transcripts and CpG-sites displaying oscillatory behavior, which were enriched with GO terms related to metabolism and development. Oscillating CpG methylation was associated with rhythmic expression of 31 transcripts. Conclusion: Although circadian oscillations may be regulated by rhythmic DNA methylation, strong rhythmic associations between transcriptome and CpG methylation were not identified. This resource constitutes a transcriptomic/epigenomic atlas of skeletal muscle and regulation of circadian rhythms.
2020-03-11 | GSE131842 | GEO
Project description:Purpose: Many mammalian genes exhibit circadian expression patterns concordant with periodic binding of transcription factors, chromatin modifications and chromosomal interactions. We determined whether lamina-associated domains (LADs) display oscillatory circadian patterns of interaction with nuclear lamin B1 during hte circadian cycle, and identified any relationship to changes in gene expression patterns in oscillatory LADs or in their vinicity. Methods: To this end, we mapped LADs by chromatin immunoprecipitation-sequencing (ChIP-seq) of lamin B1 (LMNB1) (antibody ab16048, Abcam) from mouse livers colected every 6 h, for 30 h, after entrainment of the circadian clock by 24-h fasting and refeeding. Gene expression profiles were also analyzed by RNA-sequencing (RNA-seq) at the same time points. Results and Conclusions: We report periodic interactions of chromatin domains with nuclear lamin B1, suggesting rhythmic associations of fractions of the genome with the nuclear lamina. Entrainment of the circadian clock by fasting and refeeding is accompanied in mouse liver by a gain of lamin-chromatin interactions followed by oscillations in these interactions at hundreds of lamina-associated domains (LADs). A subset of these oscillations exhibit periodicity and affect one or both LAD borders or entire stand-alone LADs. Periodic LADs are however not a dominant feature of these variable LADs, as most LADs are conserved during the circadian cycle. LAD oscillations are for the most part asynchronous between the 5’ and 3’ ends of LADs. Periodic LADs also uncoupled from gene expression patterns, periodic or not, within or in vicinity of these LADs. Accordingly, periodic genes, including central clock-control genes, are located megabases away from LADs, suggesting their residence in a transcriptionally permissive environment throughout the circadian cycle. Our data suggest autonomous oscillatory associations of fractions of the genome with the nuclear lamina, providing new evidence for rhythmic spatial configurations of chromatin. However, our data also argue that periodic LADs constitute a minor fraction of variable LADs, and reflect stochasticity in variable lamin-chromatin interactions during the circadian cycle.
2019-08-20 | GSE128675 | GEO
Project description:Oscillatory lysosomal activity for disposal of the components of the cellular clock is essential to sustain organismal circadian rhythms
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Project description:Circadian clocks are cell autonomous, transcriptionally-based, molecular mechanisms that confer the selective advantage of anticipation, enabling cells/organs to respond to environmental factors in a temporally appropriate manner. Critical to circadian clock function are two transcription factors, CLOCK and BMAL1. Previous studies in our laboratory have highlighted roles for CLOCK in cardiac physiology/pathophysiology. Here, we describe transcriptional, metabolic, and functional consequences of cardiomyocyte-specific Bmal1 knockout (CBK). Microarray analysis revealed 2037 differentially expressed genes in CBK hearts, many of which were previously identified in cardiomyocyte-specific Clock mutant (CCM) hearts. Subsequent analysis showed that Beta-hydroxybutyrate dehydrogenase 1 mRNA, protein, and enzymatic activity are markedly depressed in both CBK and CCM hearts, as is myocardial Beta-hydroxybutyrate oxidation, revealing a novel role for the circadian clock in ketone body utilization. A number of genes encoding for collagen isoforms were identified as oscillating in a time-of-day-dependent manner in wild-type, but not CBK, hearts, including col3a1, col4a1, and col4a2. Chronic induction of collagen isoform genes in CBK hearts was associated with severe age-dependent depression of cardiac function. Development of cardiomyopathy in CBK mice was associated with early mortality; all CBK mice die by one year of age. These studies highlight novel critical functions for BMAL1 in the heart, including regulation of ketone body metabolism and the extracellular matrix. RNA from whole hearts collected every 3 hours for 24 hours from wildtype and CBK mice was isolated and analyzed using MouseRef-8_V2 BeadChips (Illumina, Inc.). The 24-hour data were examined for rhythmicity using cosinor analysis and differences in rhythmicity between genotype groups were further examined for differences in the model fitting parameters.
2014-01-01 | E-GEOD-43073 | biostudies-arrayexpress
Project description:Microbiota assembly in the infant gut is influenced by time and duration of dietary exposure to breast-milk, infant formula and solid foods. In this randomized controlled intervention study, longitudinal sampling of infant stools (n=998) showed similar development of fecal bacterial communities between formula- and breast-fed infants during the first year of life (N=210). Infant formula supplemented with galacto-oligosaccharides (GOS) was most efficient to sustain high levels of bifidobacteria compared to formula containing B. longum and B. breve or placebo. Metabolite (untargeted) and bacterial profiling (16S rRNA/shallow metagenomics sequencing) revealed 24-hour oscillations and integrated data analysis identified circadian networks. Rhythmicity in bacterial diversity, specific taxa and functional pathways increased with age and was most pronounced following breast-feeding and GOS-supplementation. Circadian rhythms in dominant taxa were discovered ex-vivo in a chemostat model. Hence microbiota rhythmicity develops early in life, likely due to bacterial intrinsic clock mechanism and is affected by diet.
2024-01-10 | MSV000093802 | MassIVE
Project description:Disruption of the Circadian Clock within the Cardiomyocyte Influences Myocardial Contractie Function, Metabolism, and Gene Expression Virtually every mammalian cell, including cardiomyocytes, possesses an intrinsic circadian clock. The role of this transcriptionally-based molecular mechanism in cardiovascular biology is poorly understood. We hypothesized that the circadian clock within the cardiomyocyte influences diurnal variations in myocardial biology. We therefore generated a cardiomyocyte-specific circadian clock mutant (CCM) mouse, in order to test this hypothesis. At 12 weeks of age, CCM mice exhibit normal myocardial contractile function in vivo, as assessed by echocardiography. Radiotelemetry studies reveal attenuation of heart rate diurnal variations and bradycardia in CCM mice (in the absence of conduction system abnormalities). Reduced heart rate persisted in CCM hearts perfused ex vivo in the working mode, highlighting the intrinsic nature of this phenotype. Wild-type, but not CCM, hearts exhibited a marked diurnal variation in responsiveness to an elevation in workload (80mmHg plus 1 microM epinephrine) ex vivo, with a greater increase in cardiac power and efficiency during the dark (active) phase versus the light (inactive) phase. Moreover, myocardial oxygen consumption and fatty acid oxidation rates were increased, while cardiac efficiency was decreased, in CCM hearts. These observations were associated with no alterations in mitochondrial content or structure, and modest mitochondrial dysfunction, in CCM hearts. Gene expression microarray analysis identified 548 and 176 genes in atria and ventricles, respectively, whose normal diurnal expression patterns were altered in CCM mice. These studies suggest that the cardiomyocyte circadian clock influences myocardial contractile function, metabolism, and gene expression. Keywords: Comparison of circadian oscillations in gene expression in hearts taken from wildtype and transgenic animals
2008-01-01 | GSE10045 | GEO
Project description:By gating cell cycle progression to specific times of the day, the intracellular circadian clock is thought to reduce the exposure of replicating cells to potentially hazardous environmental and endogenous genotoxic compounds. Although core clock gene defects that eradicate circadian rhythmicity can cause an altered in vivo genotoxic stress response and aberrant proliferation rate, it remains to be determined to what extent these cell-cycle-related phenotypes are due to a cell-autonomous lack of circadian oscillations. We investigated the DNA damage sensitivity and proliferative capacity of cultured primary Cry1-/-|Cry2-/- fibroblasts. Contrasting previous in vivo studies, we show that the absence of CRY proteins does not affect the cell-autonomous DNA damage response upon exposure of primary cells in vitro to genotoxic agents, but causes cells to proliferate faster. By comparing primary wild type, Cry1-/-|Cry2-/-, Cry1+/-|Cry2-/- and Cry1-/-|Cry2+/- fibroblasts, we provide evidence that CRY proteins influence cell cycle progression in a cell-autonomous, but circadian clock-independent manner and that the accelerated cell cycle progression of Cry-deficient cells is caused by global dysregulation of Bmal1-dependent gene expression. These results suggest that the inconsistency between in vivo and in vitro observations might be attributed to systemic circadian control rather than a direct cell-autonomous control. Asynchronous proliferating MEFs grown under low (3%) oxygen tension and lysed in Trizol. Four independent cell lines were used for each genotype (WT, Cry DKO).
2011-09-30 | E-GEOD-31958 | biostudies-arrayexpress
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2009-10-22 | GSE17739 | GEO
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2023-04-11 | GSE221550 | GEO