Daily lung expression data from young and old mice
Ontology highlight
ABSTRACT: Circadian rhythms control the diurnal nature of many physiological, metabolic and immune processes. Circadian rhythms are tighly controlled by positive and negative transcriptional loops; This circuitry is altered during aging altering tissue daily function.
Project description:Circadian rhythms control the diurnal nature of many physiological, metabolic and immune processes. Circadian rhythms are tighly controlled by positive and negative transcriptional loops; This circuitry is altered during aging altering tissue daily function. We used microarrays to detail the global programme of gene expression underlying age-mediated alteration of the transcriptional progarm in lungs.
Project description:Daily rhythms in mammalian behaviour and physiology are generated by a multi-oscillator circadian system entrained through environmental cues (e.g. light and feeding). The presence of tissue niche-dependent physiological time cues has been proposed, allowing tissues the ability of circadian phase adjustment based on local signals. However, to date, such stimuli have remained elusive. Here we show that daily patterns of mechanical loading and associated osmotic challenge within physiological ranges reset circadian clock phase and amplitude in cartilage and intervertebral disc tissues in vivo and in tissue explant cultures. Hyperosmolarity (but not hypo-osmolarity) resets clocks in young and ageing skeletal tissues and induce genome-wide expression of rhythmic genes in cells. Mechanistically, RNAseq and biochemical analysis revealed the PLD2-mTORC2-AKT-GSK3β axis as a convergent pathway for both in vivo loading and hyperosmolarity-induced clock changes. These results reveal diurnal patterns of mechanical loading and consequent daily surges in osmolarity as a bona fide tissue niche-specific time cue to maintain skeletal circadian rhythms in sync.
Project description:Circadian rhythms are cell-autonomous biological oscillations with a period of about 24 hours. Current models propose that transcriptional feedback loops are the principal mechanism for the generation of circadian oscillations. In these models, Drosophila S2 cells are generally regarded as ‘non-rhythmic’ cells, as they do not express several canonical circadian components. Using an unbiased multi-omics approach, we made the surprising discovery that Drosophila S2 cells do in fact display widespread daily rhythms. Transcriptomics and proteomics analyses revealed that hundreds of genes and their products are rhythmically expressed in a 24-hour cycle. Metabolomics analyses extended these findings and illustrated that central carbon metabolism and amino acid metabolism are the main pathways regulated in a rhythmic fashion. We thus demonstrate that daily genome-wide oscillations, coupled to metabolic cycles, take place in eukaryotic cells without the contribution of known circadian regulators.
Project description:The circadian clock drives daily changes of physiology, including sleep-wake cycles, by regulating transcription, protein abundance and function. Circadian phosphorylation controls cellular processes in peripheral organs, but little is known about its role in brain function and synaptic activity. We applied advanced quantitative phosphoproteomics to mouse forebrain synaptoneurosomes isolated across 24h, accurately quantifying almost 8,000 phosphopeptides. Remarkably, half of the synaptic phosphoproteins, including numerous kinases, had large-amplitude rhythms peaking at rest-activity and activity-rest transitions. Bioinformatic analyses revealed global temporal control of synaptic function via phosphorylation, including synaptic transmission, cytoskeleton reorganization and excitatory/inhibitory balance. Remarkably, sleep deprivation abolished 98% of all phosphorylation cycles in synaptoneurosomes, indicating that sleep-wake cycles rather than circadian signals are main drivers of synaptic phosphorylation, responding to both sleep and wake pressures.
Project description:The daily pattern of temporal gene expression is regulated by the circadian clock system. Under constant environmental conditions, aging is associated with a shortening of the endogenous period of circadian rhythms in Arabidopsis. This study investigated to investigate how aging influences the waveforms of rhythmic patterns of gene expression under light/dark cycles. The waveforms of the daily cycling circadian clock showed significant warping in aged leaves, which shifted their expression pattern. Transcriptomic analysis revealed that the number of daily cycling genes in aged leaves was reduced by more than half. Furthermore, in aged plants, the expression schedule of cycling genes in both young and old leaves warped. Circadian clock mutants, including toc1, which did not exhibit age-dependent warping, had significantly altered warping patterns.
Project description:<p>Circadian clocks coordinate mammalian behaviour and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.</p><p><br></p><p><strong>LC-MS assay</strong> protocols and data are reported in the current study <strong>MTBLS1285</strong>.</p><p><strong>GC-MS assay</strong> protocols and data for this study are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1286' rel='noopener noreferrer' target='_blank'><strong>MTBLS1286</strong></a>.</p>
Project description:<p>Circadian clocks coordinate mammalian behaviour and physiology enabling organisms to anticipate 24-hour cycles. Transcription-translation feedback loops are thought to drive these clocks in most of mammalian cells. However, red blood cells (RBCs), which do not contain a nucleus, and cannot perform transcription or translation, nonetheless exhibit circadian redox rhythms. Here we show human RBCs display circadian regulation of glucose metabolism, which is required to sustain daily redox oscillations. We found daily rhythms of metabolite levels and flux through glycolysis and the pentose phosphate pathway (PPP). We show that inhibition of critical enzymes in either pathway abolished 24-hour rhythms in metabolic flux and redox oscillations, and determined that metabolic oscillations are necessary for redox rhythmicity. Furthermore, metabolic flux rhythms also occur in nucleated cells, and persist when the core transcriptional circadian clockwork is absent in Bmal1 knockouts. Thus, we propose that rhythmic glucose metabolism is an integral process in circadian rhythms.</p><p><br></p><p><strong>GC-MS assay</strong> protocols and data are reported in the current study <strong>MTBLS1286</strong>.</p><p><strong>LC-MS assay</strong> protocols and data for this study are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS1285' rel='noopener noreferrer' target='_blank'><strong>MTBLS1285</strong></a>.</p>
Project description:The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve interconnecting transcription-translation feedback loops. The hippocampus plays an important role in spatial memory and the conversion of short-term to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus, and have highlighted the importance of circadian regulation in memory formation. In this study we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry.