Collecting mouse livers for transcriptome analysis of daily rhythms.
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ABSTRACT:
SUBMITTER: Mortimer T
PROVIDER: S-EPMC8138861 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Biomedical research on mammals has traditionally neglected females, raising the concern that some scientific findings may generalize poorly to half the population. Although this lack of sex inclusion has been broadly documented, its extent within circadian genomics remains undescribed. To address this gap, we examined sex inclusion practices in a comprehensive collection of publicly available transcriptome studies on daily rhythms. Among 148 studies having samples from mammals in vivo, we found strong underrepresentation of females across organisms and tissues. Overall, only 23 of 123 studies in mice, 0 of 10 studies in rats, and 9 of 15 studies in humans included samples from females. In addition, studies having samples from both sexes tended to have more samples from males than from females. These trends appear to have changed little over time, including since 2016, when the US National Institutes of Health began requiring investigators to consider sex as a biological variable. Our findings highlight an opportunity to dramatically improve representation of females in circadian research and to explore sex differences in daily rhythms at the genome level.
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Project description:Various parasite-host interactions that involve adaptive manipulation of host behavior display time-of-day synchronization of certain events. One example is the manipulated biting behavior observed in Carpenter ants infected with Ophiocordyceps unilateralis sensu lato. We hypothesized that biological clocks play an important role in this and other parasite-host interactions. In order to identify candidate molecular clock components, we used two general strategies: bioinformatics and transcriptional profiling. The bioinformatics approach was used to identify putative homologs of known clock genes. For transcriptional profiling, RNA-Seq was performed on 48 h time courses of Ophiocordyceps kimflemingiae (a recently named species of the O. unilateralis complex), whose genome has recently been sequenced. Fungal blastospores were entrained in liquid media under 24 h light-dark (LD) cycles and were harvested at 4 h intervals either under LD or continuous darkness. Of all O. kimflemingiae genes, 5.3% had rhythmic mRNAs under these conditions (JTK Cycle, ? 0.057 statistical cutoff). Our data further indicates that a significant number of transcription factors have a peaked activity during the light phase (day time). The expression levels of a significant number of secreted enzymes, proteases, toxins and small bioactive compounds peaked during the dark phase or subjective night. These findings support a model whereby this fungal parasite uses its biological clock for phase-specific activity. We further suggest that this may be a general mechanism involved in parasite-host interactions.
| S-EPMC5669440 | biostudies-literature
Project description:Microarray transcriptome analyses of fetal mouse liver did not detect circadian expression rhythms of clock genes or clock-controlled genes, although some rhythmic transcripts that were likely not driven by endogenous cellular clocks were identified. This finding reveals a key distinction between the circadian oscillators in fetal and adult mouse livers. Thus, in this study, the transcriptomes of fetal and adult livers were systematically compared to identify differences in the gene expression profiles between these two developmental stages. Approximately 1000 transcripts were differentially enriched between the fetal and adult livers. These transcripts represent genes with cellular functions characteristic of distinct developmental stages. Clock genes were also differentially expressed between the fetal and adult livers. Developmental differences in liver gene expression might have contributed to the differences in oscillation status and functional states of the cellular circadian clock between fetal and adult livers.
| S-EPMC3283632 | biostudies-literature
Project description:Biological rhythms are widespread, allowing organisms to temporally organize their behavior and metabolism in advantageous ways. Such proper timing of molecular and cellular events is critical to their development and health. This is best understood in the case of the circadian clock that orchestrates the daily sleep/wake cycle of organisms. Temporal rhythms can also be used for spatial organization, if information from an oscillating system can be recorded within the tissue in a manner that leaves a permanent periodic pattern. One example of this is the "segmentation clock" used by the vertebrate embryo to rhythmically and sequentially subdivide its elongating body axis. The segmentation clock moves with the elongation of the embryo, such that its period sets the segment length as the tissue grows outward. Although the study of this system is still relatively young compared to the circadian clock, outlines of molecular, cellular, and tissue-level regulatory mechanisms of timing have emerged. The question remains, however, is it truly a clock? Here we seek to introduce the segmentation clock to a wider audience of chronobiologists, focusing on the role and control of timing in the system. We compare and contrast the segmentation clock with the circadian clock, and propose that the segmentation clock is actually an oscillatory ruler, with a primary function to measure embryonic space.
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Project description:We report application of RNA-seq to quantify gene expression changes in fasted mouse livers compared to re-fed controls.
2017-10-01 | GSE101596 | GEO
Project description:Objective"Hatchability" is an important economic trait in domestic poultry. Studies on poultry hatchability focus mainly on the genetic background, egg quality, and incubation conditions, whereas the molecular mechanisms behind the phenomenon that some ducklings failed to break their eggshells are poorly understood.MethodsIn this study, the transcriptional differences between the livers of normally hatched and assisted ducklings were systematically analyzed.ResultsThe results showed that the clean reads were de novo assembled into 161,804 and 159,083 unigenes (≥200-bp long) by using Trinity, with an average length of 1,206 bp and 882 bp, respectively. The defined criteria of the absolute value of log2 fold-change ≥1 and false discovery rate≤0.05 were differentially expressed and were significant. As a result, 1,629 unigenes were identified, the assisted ducklings showed 510 significantly upregulated and 1,119 significantly down-regulated unigenes. In general, the metabolic rate in the livers of the assisted ducklings was lower than that in the normal ducklings; however, compared to normal ducklings, glucose-6-phosphatase and ATP synthase subunit alpha 1 associated with energy metabolism were significantly upregulated in the assisted group. The genes involved in immune defense such as major histocompatibility complex (MHC) class I antigen alpha chain and MHC class II beta chain 1 were downregulated in the assisted ducklings.ConclusionThese data provide abundant sequence resources for studying the functional genome of the livers in ducks and other poultry. In addition, our study provided insight into the molecular mechanism by which the phenomenon of weak embryos is regulated.
| S-EPMC5411839 | biostudies-literature
Project description:Regular exercise is important for physical and mental health. An underexplored and intriguing property of exercise is its actions on the body's 24 h or circadian rhythms. Molecular clock cells in the brain's suprachiasmatic nuclei (SCN) use electrical and chemical signals to orchestrate their activity and convey time of day information to the rest of the brain and body. To date, the long-lasting effects of regular physical exercise on SCN clock cell coordination and communication remain unresolved. Utilizing mouse models in which SCN intercellular neuropeptide signaling is impaired as well as those with intact SCN neurochemical signaling, we examined how daily scheduled voluntary exercise (SVE) influenced behavioral rhythms and SCN molecular and neuronal activities. We show that in mice with disrupted neuropeptide signaling, SVE promotes SCN clock cell synchrony and robust 24 h rhythms in behavior. Interestingly, in both intact and neuropeptide signaling deficient animals, SVE reduces SCN neural activity and alters GABAergic signaling. These findings illustrate the potential utility of regular exercise as a long-lasting and effective non-invasive intervention in the elderly or mentally ill where circadian rhythms can be blunted and poorly aligned to the external world.
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Project description:In many organisms, the circadian clock drives rhythms in the transcription of clock-controlled genes that can be either circadian (?24-hr period) or ultradian (<24-hr period). Ultradian rhythms with periods that are a fraction of 24 hr are termed harmonics. Several harmonic transcripts were discovered in the mouse liver, but their functional significance remains unclear. Using a model-based analysis, we report for the first time ?7-hr third harmonic transcripts in Neurospora crassa, a well-established fungal circadian model organism. Several third harmonic genes are regulated by female fertility 7 (FF-7), whose transcript itself is third harmonic. The knockout of circadian output regulator CSP1 superimposes circadian rhythms on the third harmonic genes, whereas the knockout of stress response regulator MSN1 converts third harmonic rhythms to second harmonic rhythms. The 460 ?7-hr genes are co-regulated in two anti-phasic groups in multiple genotypes and include kinases, chromatin remodelers, and homologs of harmonic genes in the mouse liver.
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Project description:Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe-gut-brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography-mass spectrometry, nuclear magnetic resonance, and liquid chromatography-mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about "depression microbes" impacting on liver metabolism.
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Project description:Astrocytes are active partners in neural information processing [1, 2]. However, the roles of astrocytes in regulating behavior remain unclear [3, 4]. Because astrocytes have persistent circadian clock gene expression and ATP release in vitro [5-8], we hypothesized that they regulate daily rhythms in neurons and behavior. Here, we demonstrated that daily rhythms in astrocytes within the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), determine the period of wheel-running activity. Ablating the essential clock gene Bmal1 specifically in SCN astrocytes lengthened the circadian period of clock gene expression in the SCN and in locomotor behavior. Similarly, excision of the short-period CK1? tau mutation specifically from SCN astrocytes resulted in lengthened rhythms in the SCN and behavior. These results indicate that astrocytes within the SCN communicate to neurons to determine circadian rhythms in physiology and in rest activity.
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