Studying iPSCs from a hibernating mammal reveals molecular mechanisms of cold resistance in neural tissues
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE93935
PROVIDER: PRJNA362861 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5195260_1.fastq.gz | Fastqsanger.gz | |||
| SRR5195260_2.fastq.gz | Fastqsanger.gz | |||
| SRR5195261_1.fastq.gz | Fastqsanger.gz | |||
| SRR5195261_2.fastq.gz | Fastqsanger.gz | |||
| SRR5195252_1.fastq.gz | Fastqsanger.gz |
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Project description:To explore the cold resistant feature of ground squirrel neuron cells, we compared transcriptomes of human and ground squirrel iPSC derived neurons in the response to cold treatment. We identified several key pathways that are critical for the maintenance of neuronal microtubule cytoskeleton integrity at low temperature.
2018-03-22 | GSE93935 | GEO
Project description:During the winter, hibernating mammals undergo extreme changes in physiology which allow them to survive without access to food. These animals enter a state of torpor, which is characterized by a decreased metabolism, near-freezing body temperatures, and a dramatically reduced heart rate. The neurochemical basis of this regulation is largely unknown. Based on prior evidence suggesting that the peptide-rich hypothalamus plays critical roles in hibernation, we hypothesized that changes in specific cell-cell signaling peptides (neuropeptides and peptide hormones) underlie physiological changes during torpor/arousal cycles. To test this hypothesis, we used a mass spectrometry-based peptidomics approach to examine seasonal changes of endogenous peptides that occur in the hypothalamus and pituitary of a model hibernating mammal, the thirteen-lined ground squirrel (Ictidomys tridecemlineatus). In the pituitary, we observed changes in a number of distinct peptide hormones as animals prepare for torpor in October, exit torpor in March, and progress from Spring (March) to Fall (August). In the hypothalamus, we observed an overall increase in neuropeptides in October (pre-torpor), a decrease as the animal enters torpor, and an increase in a subset of neuropeptides during normothermic interbout arousals. Notable changes were observed for feeding regulatory peptides from NPY and proSAAS prohormones, opioid peptides from PENK, PDYN, and POMC prohormones, and a number of peptides without well-established functions. In contrast to transcriptome and antibody-based measurements, our mass spectrometry-based approach allowed the identification and measurement of the final processed forms of these peptides after extensive post-translational modifications. Overall, our study provides critical insight into changes in endogenous peptides in the hypothalamus and pituitary during mammalian hibernation that were not available from transcriptome measurements. Understanding the molecular basis underlying the hibernation phenotype may pave the way for future efforts to employ hibernation-like strategies for organ preservation, combating obesity, and treatments for stroke.
2023-07-10 | PXD040033 | Pride
Project description:RNA editing diversifies genomically encoded information to expand the complexity of the transcriptome. In ectothermic organisms, including Drosophila and Cephalopoda, where body temperature mirrors ambient temperature, decreases in environmental temperature lead to increases in A-to-I RNA editing and cause amino acid recoding events that are thought to be adaptive responses to temperature fluctuations. In contrast, endothermic mammals, including humans and mice, typically maintain a constant body temperature despite environmental changes. Here, A-to-I editing primarily targets repeat elements, rarely results in the recoding of amino acids and plays a critical role in innate immune tolerance. Hibernating ground squirrels provide a unique opportunity to examine RNA editing in a heterothermic mammal whose body temperature varies over 30°C and can be maintained at 5°C for many days during torpor. We profiled the transcriptome in three brain regions at six physiological states to quantify RNA editing and determine whether cold-induced RNA editing modifies the transcriptome as a potential mechanism for neuroprotection at low temperature during hibernation. We identified 5,165 A-to-I editing sites in 1,205 genes with dynamically increased editing after prolonged cold exposure. The majority (99.6%) of the cold-increased editing sites are outside of previously annotated coding regions, 82.7% lie in SINE-derived repeats, and 12 sites are predicted to recode amino acids. Additionally, A-to-I editing frequencies increase with increasing cold exposure demonstrating that ADAR remains active during torpor. Our findings suggest that dynamic A-to-I editing at low body temperature may provide a neuroprotective mechanism to limit aberrant dsRNA accumulation during torpor in the mammalian hibernator.
2018-08-09 | GSE106947 | GEO
Project description:Studying human embryonic stem cell reveals molecular mechanisms of cold resistance
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Project description:We report the application of the Illumina/Solexa sequencing-by-synthesis platform to analysis differential expression genes of two key tissues (brain and adipose tissue) during hibernation vs. aroused state, with a hibernating bat species (Myotis ricketti) as model. Total of 12272 genes were identified including 11291 genes in brain and 10691 genes in adipose tissue. Chi-square test indicated that 1943 and 3673 genes in brain and adipose tissues respectively reached the significant level (P ⤠0.01), including 1243 up-regulated and 700 down-regulated genes in hibernating brain and 2621 up-regulated and 1052 down-regulated genes in hibernating adipose tissue. This study provide opportunity to in-deep analysis the molecular mechanism of hibernating regualtion.
2018-12-31 | GSE29052 | GEO
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:We report the application of the Illumina/Solexa sequencing-by-synthesis platform to identify microRNA, which invovled in bat hibernating regualtion, in brain and adipose tissue. Total 866 microRNAs (including 477 novels) were identified and 269 microRNAs showed significant expression differences during hibernation, including 183 in brain and 199 in adipose tissue. Expressed pattern analysis indicated that two-thirds of differential expressed microRNAs showed down-regulated during hibernation in both tissues. This study will provide clules to in-deep analysis the molecular mechanism of hibernating regualtion. Identification of microRNA on hibernating regulation in 2 different tissues and 2 physiological states of bat.
2015-12-31 | E-GEOD-29053 | biostudies-arrayexpress
Project description:Objectives: While cardiac scar tissue is damaged irreversibly, hibernating myocardium is characterized by reversible contractile dysfunction. Limited data are available in humans regarding the molecular biology of hibernating myocardium. The aim of this study was to identify new molecular mechanisms distinctive for human hibernating myocardium by gene expression analysis. Results: Of 4,171 transcripts examined, we identified 86 to be differentially expressed. Twentyone genes showed an increased and 65 genes a decreased expression in hibernating myocardium. Functional clustering revealed major changes in the expression of genes associated with transcription, protein modification and phosphorylation, regulation of apoptosis and intercellular communication. Besides the reported upregulation of ß-adrenergic receptor kinase-1 in heart failure, we observed new gene expression patterns, such as the upregulation of fas-activated serine/threonine kinase (FAST) or reduced expression of desmoplakin. Downregulation of desmoplakin in cardiomyocytes from hibernating myocardium was also seen on the protein level, consistent with a role of this protein in the development of a dilative cardiomyopathy. Conclusions: Gene expression analysis of hibernating myocardium provided novel insights into the molecular mechanisms underlying ischemic heart failure. Dysfunction of desmosomes may contribute to impaired contractility and dilative tissue remodeling. Keywords: disease state analysis
2007-07-01 | GSE4704 | GEO
Project description:We report the application of the Illumina/Solexa sequencing-by-synthesis platform to identify microRNA, which invovled in bat hibernating regualtion, in brain and adipose tissue. Total 866 microRNAs (including 477 novels) were identified and 269 microRNAs showed significant expression differences during hibernation, including 183 in brain and 199 in adipose tissue. Expressed pattern analysis indicated that two-thirds of differential expressed microRNAs showed down-regulated during hibernation in both tissues. This study will provide clules to in-deep analysis the molecular mechanism of hibernating regualtion.
2015-12-31 | GSE29053 | GEO
Project description:we investigated transcriptomes of H1 ESCs in the response to cold treatment.
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