Liver transcriptomic and methylomic analyses identify transcriptional MAPK regulation in facultative hibernation of Syrian hamster
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ABSTRACT:
ORGANISM(S): Mesocricetus auratus
PROVIDER: GSE199817 | GEO | 2023/05/02
REPOSITORIES: GEO
Similar Datasets
Project description:Hibernation consist of alternating torpor/arousal phases, during which animals cope with repetitive hypothermia and ischemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole genome bisulfite sequencing in liver of hibernating Syrian hamster (Mesocricetus auratus). Gene Ontology analysis was performed on 844 differentially expressed genes (DEGs) and confirmed the shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. We show a so far unreported suppression of MAPK and PP1 pathways. Notably, hibernating hamsters showed upregulation of MAPK inhibitors (DUSPs and SPRYs) and reduced levels of MAPK induced transcription factors. Promoter methylation was found to modulate the expression of genes targeted by these transcription factors. In conclusion, we document gene regulation between hibernation phases, which may aid the identification of pathways and targets to prevent organ damage in transplantation or ischemia-reperfusion.
2023-05-02 | GSE199815 | GEO
Project description:Hibernation consist of alternating torpor/arousal phases, during which animals cope with repetitive hypothermia and ischemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole genome bisulfite sequencing in liver of hibernating Syrian hamster (Mesocricetus auratus). Gene Ontology analysis was performed on 844 differentially expressed genes (DEGs) and confirmed the Liver, shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. We Liver, show a so far unreported suppression of MAPK and PP1 pathways. Notably, hibernating hamsters Liver, showed upregulation of MAPK inhibitors (DUSPs and SPRYs) and reduced levels of MAPK induced transcription factors. Promoter methylation was found to modulate the expression of genes targeted by these transcription factors. In conclusion, we document gene regulation between hibernation phases, which may aid the identification of pathways and targets to prevent organ damage in transplantation or ischemia-reperfusion.
2023-05-02 | GSE199814 | GEO
Project description:Liver transcriptomic and methylomic analyses identify transcriptional MAPK regulation in facultative hibernation of Syrian hamster
| PRJNA821531 | ENA
Project description:Liver transcriptomic and methylomic analyses identify transcriptional MAPK regulation in facultative hibernation of Syrian hamster [WGBS]
| PRJNA821535 | ENA
Project description:Liver transcriptomic and methylomic analyses identify transcriptional MAPK regulation in facultative hibernation of Syrian hamster [RNA-Seq]
| PRJNA821536 | ENA
Project description:Hibernation is an adaptive strategy for surviving during periods with little or no food availability, by profoundly reducing the metabolic rate and the core body temperature (T b). Obligate hibernators (e.g. bears, ground squirrels, etc.) hibernate every winter under the strict regulation of endogenous circannual rhythms, and they are assumed to undergo adaptive remodelling in autumn, the pre-hibernation period, prior to hibernation. However, little is known about the nature of pre-hibernation remodelling. Syrian hamsters (Mesocricetus auratus) are facultative hibernators that can hibernate irrespective of seasons when exposed to prolonged short photoperiod and cold ambient temperature (SD-Cold) conditions. Their T b set point reduced by the first deep torpor (DT) and then increased gradually after repeated cycles of DT and periodic arousal (PA), and finally recovered to the level observed before the prolonged SD-Cold in the post-hibernation period. We also found that, before the initiation of hibernation, the body mass of animals decreased below a threshold, indicating that hibernation in this species depends on body condition. These observations suggest that Syrian hamsters undergo pre-hibernation remodelling and that T b and body mass can be useful physiological markers to monitor the remodelling process during the pre-hibernation period.
| S-EPMC4852639 | biostudies-literature
Project description:Dyslipidemia has been widely proven to contribute to cardiovascular diseases and other metabolic disorders, especially in insulin resistance and type 2 diabetes. The overproduction of VLDL is a significant characteristic of dyslipidemia, indicating the dysfunction of hepatic lipid metabolism, from triglyceride synthesis to transport. The fructose-fed Syrian golden hamster is an established animal model for the study of VLDL assembly with insulin resistance, however, it remains unknown how VLDL production is regulated at the transcriptional level due to the absence of a complete hamster genome. Here, we performed deep sequencing and constructed an mRNA-miRNA-lncRNA interaction network of Syrian golden hamster liver in order to reveal the global transcription profile and find potential RNA molecular regulation of VLDL production. We identified 4,450 novel multi-exon hamster lncRNAs and 755 miRNAs expressed in liver. Additionally, 146 differentially expressed coding genes, 27 differentially expressed lncRNA genes, as well as 16 differentially expressed miRNAs were identified. We then constructed an mRNA-miRNA-lncRNA interaction network that may potentially regulate VLDL production, and interestingly found several microRNA-centered regulatory networks. In order to verify our interpretation, miR-486 was selected for further experiments. Overexpression or down-regulation of miR-486 in fructose-fed hamsters resulted in altered hepatic expression of proteins involved in VLDL production, and in modulated levels of circulating VLDL. Our findings implicated that miR-486 is a potential regulator of circulating VLDL levels. These results provide new insights and a valuable resource for further study of the molecular mechanisms of VLDL secretion.
| S-EPMC5010245 | biostudies-literature
Project description:Glioma is the most malignant and aggressive type of brain tumour with high heterogeneity and mortality. Although some clinicopathological factors have been identified as prognostic biomarkers, the individual variants and risk stratification in patients with lower grade glioma (LGG) have not been fully elucidated. The primary aim of this study was to identify an efficient DNA methylation combination biomarker for risk stratification and prognosis in LGG. We conducted a retrospective cohort study by analysing whole genome DNA methylation data of 646 patients with LGG from the TCGA and GEO database. Cox proportional hazard analysis was carried out to screen and construct biomarker model that predicted overall survival (OS). The Kaplan-Meier survival curves and time-dependent ROC were constructed to prove the efficiency of the signature. Then, another independent cohort was used to further validate the finding. A two-CpG site DNA methylation signature was identified by multivariate Cox proportional hazard analysis. Further analysis indicated that the signature was an independent survival predictor from other clinical factors and exhibited higher predictive accuracy compared with known biomarkers. This signature was significantly correlated with immune-checkpoint blockade, immunotherapy-related signatures and ferroptosis regulator genes. The expression pattern and functional analysis showed that these two genes corresponding with two methylation sites contained in the model were correlated with immune infiltration level, and involved in MAPK and Rap1 signalling pathway. The signature may contribute to improve the risk stratification of patients and provide a more accurate assessment for precision medicine in the clinic.
| S-EPMC8743658 | biostudies-literature
Project description:Mammalian hibernators store fat extensively in white adipose tissues (WATs) during pre-hibernation period (Pre-HIB) to prepare for hibernation. However, the molecular mechanisms underlying the pre-hibernation remodeling of WAT have not been fully elucidated. Syrian hamsters, a food-storing hibernator, can hibernate when exposed to a winter-like short day photoperiod and cold ambient temperature (SD-Cold). Animals subjected to prolonged SD-Cold had smaller white adipocytes and beige-like cells within subcutaneous inguinal WAT (iWAT). Time-course analysis of gene expression with RNA-sequencing and quantitative PCR demonstrated that the mRNA expression of not only genes involved in lipid catabolism (lipolysis and beta-oxidation) but also lipid anabolism (lipogenesis and lipid desaturation) was simultaneously up-regulated prior to hibernation onset in the animals. The enhanced capacity of both lipid catabolism and lipid anabolism during hibernation period (HIB) is striking contrast to previous observations in fat-storing hibernators that only enhance catabolism during HIB. The mRNA expression of mTORC1 and PPAR signaling molecules increased, and pharmacological activation of PPARs indeed up-regulated lipid metabolism genes in iWAT explants from Syrian hamsters. These results suggest that the Syrian hamster rewires lipid metabolisms while preparing for hibernation to effectively utilize body fat and synthesize it from food intake during HIB.
| S-EPMC6360343 | biostudies-literature
Project description:Previous studies have identified differences in DNA methylation in autistic individuals compared to neurotypical individuals. Yet, it is unclear if this extends to autistic traits-subclinical manifestation of autism features in the general population. Here, we investigate the association between DNA methylation at birth (cord blood), and scores on the Social and Communication Disorders Checklist (SCDC), a measure of autistic traits, in 701 8-year-olds, by conducting a methylome-wide association study (MWAS). We did not identify significant CpGs associated with SCDC. The most significant CpG site was cg14379490, on chromosome 9 (MWAS beta?=?-?1.78?±?0.35, p value?=?5.34?×?10 -7 ). Using methylation data for autism in peripheral tissues, we did not identify a significant concordance in effect direction of CpGs with p value <?10-4 in the SCDC MWAS (binomial sign test, p value >?0.5). In contrast, using methylation data for autism from post-mortem brain tissues, we identify a significant concordance in effect direction of CpGs with a p value <?10-4 in the SCDC MWAS (binomial sign test, p value?=?0.004). Supporting this, we observe an enrichment for genes that are dysregulated in the post-mortem autism brain (one-sided Wilcoxon rank-sum test, p value?=?6.22?×?10-5). Finally, integrating genome-wide association study (GWAS) data for autism (n?=?46,350) with mQTL maps from cord-blood (n?=?771), we demonstrate that mQTLs of CpGs associated with SCDC scores at p value thresholds of 0.01 and 0.005 are significantly shifted toward lower p values in the GWAS for autism (p?<?5?×?10-3). We provide additional support for this using a GWAS of SCDC, and demonstrate a lack of enrichment in a GWAS of Alzheimer's disease. Our results highlight the shared cross-tissue methylation architecture of autism and autistic traits, and demonstrate that mQTLs associated with differences in DNA methylation associated with childhood autistic traits are enriched for common genetic variants associated with autism and autistic traits.
| S-EPMC6637466 | biostudies-literature