Studying iPSCs from a hibernating mammal reveals molecular mechanisms of cold resistance in neural tissues
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA362861
ORGANISM(S): Ictidomys tridecemlineatus Homo sapiens
PROVIDER: GSE93935 | GEO | 2018/03/22
REPOSITORIES: GEO
Similar Datasets
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: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:Studying iPSCs from a hibernating mammal reveals molecular mechanisms of cold resistance in neural tissues
| PRJNA362861 | ENA
Project description:Mammalian hibernation is a dramatic physiological transition that involves the controlled reduction of regulated body temperature and the consequent depression of all physiological processes. The resulting reduction of metabolism and associated energy expenditure permits survival during extended periods of poor food availability in winter. To date our understanding of the molecular events that give rise to the hibernating phenotype is fragmentary and incomplete. Here, we present a large-scale gene expression screen to explore the transcriptional changes that are associated with the torpid phenotype of the hibernating golden-mantled ground squirrel, Spermophilus lateralis. Expression profiles for liver, cardiac tissue, and brain isolated from summer active, torpid, and interbout aroused animals were generated by hybridization to a squirrel microarray composed of >12,000 cDNA probes. We reveal that the transcriptional changes associated with torpor are modest and generally involve less than 2-fold changes in mRNA level. By profiling the distribution of gene ontological terms in the lists of differentially expressed genes we were able to identify the functional themes that distinguish the summer awake and hibernating phenotypes. In all tissues, the pattern of differential gene expression is consistent with a switch to lipid metabolism during hibernation. In liver, we detected an expression signature suggestive of a profound depression in urea metabolism and detoxification pathways. This expression signature was reproduced in transcript data collected from liver of the13-lined ground squirrel, S. tridecemlineatus, suggesting that this phenotype is conserved between closely related species. The transcriptional changes in cardiac tissue were interpreted as a component of the bradycardia associated with torpor. The function of the differentially expressed transcripts in brain is less transparent, likely due to heterogeneity among the responses of different cell populations in this complex organ.
2010-06-05 | E-GEOD-2033 | biostudies-arrayexpress
Project description:Mammalian hibernation is a dramatic physiological transition that involves the controlled reduction of regulated body temperature and the consequent depression of all physiological processes. The resulting reduction of metabolism and associated energy expenditure permits survival during extended periods of poor food availability in winter. To date our understanding of the molecular events that give rise to the hibernating phenotype is fragmentary and incomplete. Here, we present a large-scale gene expression screen to explore the transcriptional changes that are associated with the torpid phenotype of the hibernating golden-mantled ground squirrel, Spermophilus lateralis. Expression profiles for liver, cardiac tissue, and brain isolated from summer active, torpid, and interbout aroused animals were generated by hybridization to a squirrel microarray composed of >12,000 cDNA probes. We reveal that the transcriptional changes associated with torpor are modest and generally involve less than 2-fold changes in mRNA level. By profiling the distribution of gene ontological terms in the lists of differentially expressed genes we were able to identify the functional themes that distinguish the summer awake and hibernating phenotypes. In all tissues, the pattern of differential gene expression is consistent with a switch to lipid metabolism during hibernation. In liver, we detected an expression signature suggestive of a profound depression in urea metabolism and detoxification pathways. This expression signature was reproduced in transcript data collected from liver of the13-lined ground squirrel, S. tridecemlineatus, suggesting that this phenotype is conserved between closely related species. The transcriptional changes in cardiac tissue were interpreted as a component of the bradycardia associated with torpor. The function of the differentially expressed transcripts in brain is less transparent, likely due to heterogeneity among the responses of different cell populations in this complex organ. Keywords: other
2004-12-03 | GSE2033 | GEO
Project description:Mammalian hibernation is a strategy employed by many species to survive fluctuations in resource availability and environmental conditions. Hibernating mammals endure conditions of dramatically depressed heart rate, body temperature, and oxygen consumption; yet show no typical pathological response. Because of the high abundance and metabolic cost of skeletal muscle, not only must it adjust to the constraints of hibernation, but is positioned to play a more active role in the initiation and maintenance of the hibernation phenotype. In this study, MS/MS proteomic data were searched against a custom database of transcriptomic and genomic protein predictions built using the platform GalaxyP. This proteogenomic approach allows for a thorough investigation of skeletal muscle protein expression throughout the circannual cycle of the 13-lined ground squirrel. Of the 1,563 proteins identified by these methods, 232 were differentially expressed. Not only do these data support previously reported physiological transitions, they also offer insight into specific mechanisms of how their muscles might be reducing nitrogenous waste, preserving mass and function, and signaling to other tissues. Additionally, the combination of proteomic and transcriptomic data provides unique opportunities for determining the level of post-transcriptional regulation throughout the year and improving the genomic annotation of this non-model organism.
2018-07-11 | PXD003188 | Pride
Project description:This series represents the heart transcriptome for animals sampled during summer, interbout arousal, and late torpor Keywords = squirrel, heart, hibernation Keywords: other
2004-12-03 | GSE2023 | GEO
Project description:This series represents the liver transcriptome for animals sampled during summer, interbout arousal, and late torpor Keywords = squirrel, liver, hibernation Keywords: other
2004-12-03 | GSE2021 | GEO
Project description:Hibernation in mammals such as the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) takes place over 4 to 6 months and is characterized by multi-day bouts of hypothermic torpor (5-7 °C core body temperature) that are regularly interrupted every 1-2 weeks by brief (12-24 hour) normothermic arousal periods called interbout arousals. The goal of our work was to identify the molecular mechanisms which underlie the hibernator’s ability to preserve heart function and avoid the deleterious effects of skeletal muscle disuse atrophy over prolonged periods of inactivity, starvation, and near-freezing body temperatures. To achieve this goal, we performed organelle enrichment of heart and skeletal muscle at five seasonal time points followed by LC-MS-based label-free quantitative proteomics. In both organs we saw a dramatic increase in levels of many proteins as ground squirrels transition from an active state in September to a pre-hibernation state in October. Interestingly, seasonal abundance patterns also identified new candidates for mitigating disuse atrophy in skeletal muscle which include higher levels of DHRS7C, SRL, and RTN2 in December-January torpid, IBA, and March active animals; and higher March active levels of TRIM72 and MPZ. Elevation of these proteins prompted us to perform an ex vivo contractile mechanics analysis of both type 1 (soleus) and type 2 (extensor digitorum longus) muscles in fall active, torpid, and spring active animals. Consistent with our hypotheses, both muscle types showed no deleterious effects despite several months of sedentary activity that would normally result in reduced muscle performance in non-hibernating mammals. An increased understanding of protein expression in natural hibernators may enable novel therapeutic strategies to treat human health concerns such as muscle disuse atrophy and heart disease.
2023-12-21 | PXD044532 | Pride
Project description:We report RNA-Seq experiments of eye and retinal tissues from Ground Squirrel (Ictidomys tridecemlineatus)
2016-09-12 | GSE84931 | GEO