GRO-seq analysis of liver gene transcription in hibernating 13-lined ground squirrels
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PROVIDER: PRJNA700632 | ENA |
REPOSITORIES: ENA
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Project description:Hibernating mammals undergo a dramatic drop in temperature and blood flow during torpor and must suppress hemostasis to avoid stasis blood clotting. In addition, cold storage of most mammalian platelets induces cold storage lesions, resulting in rapid clearance following transfusion. 13-lined ground squirrels (Ictidomys tridecemlineatus) provide a model to study hemostasis and cold storage of platelets during hibernation because, even with a body temperature of 4-8C, their platelets are resistant to cold storage lesions. We quantified and systematically compared proteomes of platelets collected from ground squirrels at summer (activity), fall (entrance), and winter (topor) to elucidate how molecular-level changes in platelets may support hemostatic adaptations in torpor. Platelets were isolated from squirrel blood collected in June, October, and January. Platelet lysates from each animal were digested with trypsin prior to 11-plex tandem mass tag (TMT) labeling, followed by LC-MS/MS analysis for relative protein quantification. We found over 700 platelet proteins with significant changes over the course of entrance, torpor, and activity – including systems of proteins regulating translation, platelet degranulation, metabolism, complement, and coagulation cascades. We also noted species specific differences in hemostatic, secretory, and inflammatory regulators in ground squirrel platelets relative to human platelets. In addition to providing the first ever proteomic characterization of platelets from hibernating animals, our results support a model whereby systematic changes in metabolic, hemostatic, and other proteins support physiological adaptations in torpor. In addition, our results could translate into better methods to cold store human platelets, increasing their supply and quality for transfusions.
2021-12-08 | PXD026903 | Pride
Project description:Hibernators dramatically lower metabolism to save energy while fasting for months. Prolonged fasting challenges metabolic homeostasis, yet small-bodied hibernators emerge each spring ready to resume all aspects of active life, including immediate reproduction. The liver is the body’s metabolic hub, processing and detoxifying macromolecules to provide essential fuels to brain, muscle and other organs throughout the body. Here we quantify changes in liver gene expression using RNA-seq to measure the steady-state transcriptome and GRO-seq to measure transcription across several distinct physiological states of hibernation in 13-lined ground squirrels. Our data capture key timepoints in both the seasonal and torpor-arousal cycles of hibernation. Strong positive correlation between transcription and the transcriptome indicates that transcriptional control dominates the known seasonal reprogramming of metabolic gene expression in liver for hibernation. During the torpor-arousal cycle, however, discordance develops between transcription and the steady-state transcriptome by at least two mechanisms: 1) although not transcribed during torpor, some liver transcripts are unusually stable, consistent with data from other tissues; and 2) unexpectedly, on some genes, we document continuing, slow elongation with a failure to terminate transcription across the torpor bout. While the steady-state RNAs corresponding to these readthrough transcripts did not increase during torpor, they did increase shortly after rewarming despite then low transcription. Both of these mechanisms assure the availability of functional transcripts immediately upon rewarming. Integration of transcriptional, post-transcriptional and RNA stability control mechanisms, all demonstrated in these data, likely initiate a serial gene expression program across the short euthermic period that restores the tissue and prepares the animal for the next bout of torpor.
2021-05-10 | GSE166370 | GEO
Project description:Mammalian hibernation is characterized by metabolic rate depression and a strong decrease in core body temperature that together create energy savings such that most species do not have to eat over the winter months. Brown adipose tissue (BAT), a thermogenic tissue that uses uncoupled mitochondrial respiration to generate heat instead of ATP, plays a major role in rewarming from deep torpor. The present study used label-free phosphoproteomics to investigate changes in BAT from thirteen-lined ground squirrels (Ictidomys tridecemlineatus), comparing euthermic squirrels with squirrels in deep torpor. Differential expression of mitochondrial proteins was also investigated. Surprisingly, mitochondrial membrane and matrix protein expression in BAT was largely constant between active euthermic squirrels and their hibernating counterparts. Validation by immunoblotting confirmed that the protein levels of mitochondrial respiratory chain complexes were largely unchanged. However, phosphoproteomics showed that pyruvate dehydrogenase (PDH) phosphorylation increased during ground squirrel hibernation, and this was confirmed by immunoblotting with phospho-specific antibodies. PDH phosphorylation leads to its inactivation, which suggests that BAT carbohydrate oxidation is inhibited during hibernation. Phosphorylation of hormone-sensitive lipase (HSL) also increased during hibernation, suggesting that HSL would be in a partly activated state in BAT to produce the fatty acids that are likely the primary fuel for thermogenesis during arousal.
2017-07-11 | PXD004261 | Pride
Project description:Hibernation is energy saving adaptation involving suppression of activity to survive in highly seasonal environments. Immobility and disuse generate muscle loss in most mammalian species. In contrast to other mammals, bears and ground squirrels demonstrate limited muscle atrophy over the physical inactivity of winter hibernation. This suggests that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional program underlying molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screening in hind limb muscles comparing hibernating and summer active black bears and arctic ground squirrels by the use of custom 9,600 probe cDNA microarrays. The molecular pathway analysis showed an elevated proportion of overexpressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during hibernation that implies induction of translation at different hibernation states. The induction of protein biosynthesis likely contributes to attenuation of disuse muscle atrophy through prolonged periods of immobility and starvation. This adaptive mechanism allows hibernating mammals to maintain full musculoskeletal function and preserve mobility during and immediately after hibernation, thus promoting survival. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction of multiply genes involved in oxidation reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation. Arctic ground squirrels sampled during winter hibernation were compared with the animals sampled during summer. Muscle was hybridized on a custom 9,600 probes nylon membrane microarray platform. Ten in late torpor, four in early arousal, then in late arousal were studied in experiments.
2014-10-16 | E-GEOD-62377 | biostudies-arrayexpress
Project description:Hibernation is a seasonally adaptive strategy that allows hibernators to live through extreme cold condition and was viewed as a highly regulated physiological event. In spite of the profound reduction of blood flow to retina, hibernation causes no lasting retinal injury and hibernators show increased tolerance to ischemic insults during hibernation period. To understand the molecular changes of retina in response to hibernation we applied transcriptomic analysis to explore the changes of gene expression of 13-lined ground squirrel retinas during hibernation.
2017-06-05 | GSE93685 | GEO
Project description:Hibernation is energy saving adaptation involving suppression of activity to survive in highly seasonal environments. Immobility and disuse generate muscle loss in most mammalian species. In contrast to other mammals, bears and ground squirrels demonstrate limited muscle atrophy over the physical inactivity of winter hibernation. This suggests that hibernating mammals have adaptive mechanisms to prevent disuse muscle atrophy. To identify common transcriptional program underlying molecular mechanisms preventing muscle loss, we conducted a large-scale gene expression screening in hind limb muscles comparing hibernating and summer active black bears and arctic ground squirrels by the use of custom 9,600 probe cDNA microarrays. The molecular pathway analysis showed an elevated proportion of overexpressed genes involved in all stages of protein biosynthesis and ribosome biogenesis in muscle of both species during hibernation that implies induction of translation at different hibernation states. The induction of protein biosynthesis likely contributes to attenuation of disuse muscle atrophy through prolonged periods of immobility and starvation. This adaptive mechanism allows hibernating mammals to maintain full musculoskeletal function and preserve mobility during and immediately after hibernation, thus promoting survival. The lack of directional changes in genes of protein catabolic pathways does not support the importance of metabolic suppression for preserving muscle mass during winter. Coordinated reduction of multiply genes involved in oxidation reduction and glucose metabolism detected in both species is consistent with metabolic suppression and lower energy demand in skeletal muscle during inactivity of hibernation.
2014-10-16 | GSE62377 | GEO
Project description:miRNA profiling of miRNAs in Hibernating Arctic Ground Squirrels
| PRJNA122077 | ENA
Project description:Differential gene expression in a wide range of tissues including brown adipose tissue (BAT), liver, heart, hypothalamus, and skeletal muscle in hibernating arctic ground squirrels during multiple stages in torpor-arousal cycles compared to non-hibernating (post-reproductive) animals with illumina beadarray technology. Keywords: Multiple stage comparison
2006-08-03 | GSE5414 | GEO
Project description:Hibernation is an energy-saving strategy adopted by a wide range of mammals to survive highly seasonal or unpredictable environments. Arctic ground squirrels living in Alaska provide an extreme example, with 6-9 months long hibernation seasons when body temperature alternates between levels near 0 C during torpor and 37 C during arousal episodes. Heat production during hibernation is provided, in part, by non-shivering thermogenesis that occurs in large deposits of brown adipose tissue (BAT). BAT is active at tissue temperatures from 0 to 37 C during rewarming and continuously at near 0 C during torpor in subfreezing conditions. Despite its crucial role in hibernation, the global gene expression patterns in BAT during hibernation compared to the non-hibernation season remain largely unknown. We report a large-scale study of differential gene expression in BAT between winter hibernating and summer active arctic ground squirrels using mouse microarrays. Selected differentially expressed genes identified on the arrays were validated by quantitative real-time PCR using ground squirrel specific primers. Our results show that the mRNA levels of the genes involved in nearly every step of the biochemical pathway leading to non-shivering thermogenesis are significantly increased in BAT during hibernation, whereas those of genes involved in protein biosynthesis are significantly decreased compared to the summer active animals in August. The differentially expressed genes also include those involved in adipose differentiation, substrate transport, and structure remodeling, which may enhance thermogenesis at low tissue temperatures in BAT. Keywords: hibernating animals vs. summer active animals
2005-10-21 | GSE3426 | GEO
Project description:Differential gene expression in a wide range of tissues including brown adipose tissue (BAT), liver, heart, hypothalamus, and skeletal muscle in hibernating arctic ground squirrels during multiple stages in torpor-arousal cycles compared to non-hibernating (post-reproductive) animals with illumina beadarray technology. Arctic Ground Squirrels were sampled at four stages of hibernation: early arousal denoted as EA (1-2 hrs after Tb cross 30¡C, n=4), late arousal denoted as LA (7-8 hrs after Tb cross 30¡C, n=4), early torpor denoted as ET (10-20% of torpid episode, n=4) and late torpor denoted as LT (80-90% of torpid episode, n=5), where Tb is the body temperature and the length of torpid episode is estimated from the previous torpor bout. Post-reproductive animals denoted as PR (n=7) were used as non-hibernating control. Five tissue types: brown adipose tissue (BAT), liver, heart, hypothalamus, and skeletal muscle were hybridized on two customized 700-gene beadarray platforms: 1A and 2A on 96-sample Illumina ArrayMatrix. The data of a pilot study involving brown adipose tissue (BAT), liver, and skeletal muscle on 16-sample Illumina BeadChip denoted as 16chip are also included in this series.
2010-07-01 | E-GEOD-5414 | biostudies-arrayexpress