Remodeling of gene expression during C. elegans hibernation. [Ribo-Seq]
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ABSTRACT:
PROVIDER: PRJNA1122590 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29365039.fastq.gz | Fastqsanger.gz | |||
| SRR29365040.fastq.gz | Fastqsanger.gz | |||
| SRR29365041.fastq.gz | Fastqsanger.gz | |||
| SRR29365042.fastq.gz | Fastqsanger.gz | |||
| SRR29365043.fastq.gz | Fastqsanger.gz |
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Project description:Remodeling of gene expression during C. elegans hibernation. [RNA-Seq]
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Project description:In the wild, many animals respond to cold temperatures by entering hibernation. In the clinic, controlled cooling is used widely in transplantation and emergency medicine. Yet, the molecular mechanisms the cells use in response to cold remain largely unexplored. One aspect of cold adaptation is a global downregulation of protein synthesis. Here, we performed total RNA sequencing combined with ribosome profiling to assess specific mRNA levels and their translational status during Caenorhabditis elegans hibernation.
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Project description:Mammalian hibernators display phenotypes similar to physiological conditions in non-hibernating species under conditions of calorie restriction and fasting, hypoxia, hypothermia, ischemia-reperfusion, and sleep. However, whether or how similarities are also reflected on molecular and genetic levels is unclear. We identified molecular signatures of torpor and arousal in hibernation using a new custom-designed cDNA microarray for the arctic ground squirrel (Urocitellus parryii,) and compared them to molecular signatures of selected phenotypes in mouse. Our results show that differential gene expression related to metabolism during torpor is closely related to that during calorie restriction and hypoxia. PPARM-NM-1 is crucial for metabolic remodeling in hibernation. Genes related to the sleep-wake cycle and temperature response genes induced by hypothermia follow the same expression changes as in torpor-arousal cycle. Increased fatty acid metabolism might contribute to the protection against ischemia-reperfusion injury during hibernation. Further, by comparing with thousands of pharmacological signatures, we identified drugs that may induce similar expression patterns in human cell lines as during hibernation. Arctic ground squirrels sampled during winter hibernation were compared with the animals sampled during summer. Liver was hybridized on a custom 9,600 probes nylon membrane microarray platform. Four squirrels in early torpor, five in late torpor, four in early arousal, four in late arousal, and seven in summer active were studied in experiments.
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Project description:Mammalian hibernators display phenotypes similar to physiological conditions in non-hibernating species under conditions of calorie restriction and fasting, hypoxia, hypothermia, ischemia-reperfusion, and sleep. However, whether or how similarities are also reflected on molecular and genetic levels is unclear. We identified molecular signatures of torpor and arousal in hibernation using a new custom-designed cDNA microarray for the arctic ground squirrel (Urocitellus parryii,) and compared them to molecular signatures of selected phenotypes in mouse. Our results show that differential gene expression related to metabolism during torpor is closely related to that during calorie restriction and hypoxia. PPARα is crucial for metabolic remodeling in hibernation. Genes related to the sleep-wake cycle and temperature response genes induced by hypothermia follow the same expression changes as in torpor-arousal cycle. Increased fatty acid metabolism might contribute to the protection against ischemia-reperfusion injury during hibernation. Further, by comparing with thousands of pharmacological signatures, we identified drugs that may induce similar expression patterns in human cell lines as during hibernation.
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Project description:In mammals, loss of food intake and reduced mechanical loading/activity of skeletal muscles leads to a very rapid loss in mass and function. However, during hibernation in bears, despite spending months without feeding and with very modest muscle activity, only moderate muscle wasting is observed. Part of this tissue sparing is due to a highly reduced metabolic activity in almost all tissues, including skeletal muscle. Interestingly, myosin, one of the most abundant proteins in skeletal muscle, can have different metabolic activities in inactive muscle. Therefore, to evaluate the functional and metabolic alterations in hibernating muscles, we performed an analysis on a single muscle fiber level. Individual fibers were taken from biopsies of the same bears either during hibernation or during the active phase in the summer. We confirm that muscle fibers from hibernating bears show no loss of fiber size and a mild reduction in force generating capacity. However, ATPase activity of single muscle fibers taken from hibernating bears show a significant reduction in ATPase activity, which is due to a reduced ATP turnover by myosin. By performing a single fiber proteomics analysis, we could determine in a fiber type specific manner that muscle fibers undergo a major remodeling of their proteome. Both type 2A and type 1/2A mixed fibers show a marked reduction in mitochondrial proteins during hibernation, with a decrease in proteins linked to the TCA cycle and mitochondrial translation.
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Project description:Hibernation enables many species of the mammalian kingdom to overcome periods of harsh environmental conditions. During this physically inactive state metabolic rate and body temperature are drastically downregulated, thereby reducing energy requirements (torpor) also over shorter time periods. Since blood cells reflect the organism's current condition, it was suggested that transcriptomic alterations in blood cells mirror the torpor-associated physiological state. Transcriptomics on blood cells of torpid and non-torpid Djungarian hamsters and QIAGEN Ingenuity Pathway Analysis (IPA) revealed key target molecules (TMIPA), which were subjected to a comparative literature analysis on transcriptomic alterations during torpor/hibernation in other mammals. Gene expression similarities were identified in 148 TMIPA during torpor nadir among various organs and phylogenetically different mammalian species. Based on TMIPA, IPA network analyses corresponded with described inhibitions of basic cellular mechanisms and immune system-associated processes in torpid mammals. Moreover, protection against damage of heart, kidney, and liver was deduced from this gene expression pattern in blood cells. This study shows that blood cell transcriptomics can reflect the general physiological state during torpor nadir. Furthermore, the understanding of molecular processes for torpor initiation and organ preservation may have beneficial implications for humans in extremely challenging environments, such as in medical intensive care units and in space.
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