Department of Data Analysis and Mathematical Modelling, Faculty of Bioscience Engineering, Ghent University, B-9000 Ghent, Belgium.
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands.
Proc Biol Sci. 2023 May 31;290(1999):20230368. doi: 10.1098/rspb.2023.0368. Epub 2023 May 24.
Hibernation consists of alternating torpor-arousal phases, during which animals cope with repetitive hypothermia and ischaemia-reperfusion. Due to limited transcriptomic and methylomic information for facultative hibernators, we here conducted RNA and whole-genome bisulfide sequencing in liver of hibernating Syrian hamster (). Gene ontology analysis was performed on 844 differentially expressed genes and confirmed the shift in metabolic fuel utilization, inhibition of RNA transcription and cell cycle regulation as found in seasonal hibernators. Additionally, we showed a so far unreported suppression of mitogen-activated protein kinase (MAPK) and protein phosphatase 1 pathways during torpor. Notably, hibernating hamsters showed upregulation of MAPK inhibitors (dual-specificity phosphatases and sproutys) and reduced levels of MAPK-induced transcription factors (TFs). Promoter methylation was found to modulate the expression of genes targeted by these TFs. 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 ischaemia-reperfusion.
冬眠由交替的昏睡-觉醒阶段组成,在此期间动物会应对反复的低温和缺血再灌注。由于兼性冬眠动物的转录组和甲基组信息有限,我们在此对冬眠叙利亚仓鼠的肝脏进行了 RNA 和全基因组亚硫酸氢盐测序()。对 844 个差异表达基因进行了基因本体分析,证实了代谢燃料利用、RNA 转录抑制和细胞周期调控的转变,这在季节性冬眠动物中也有发现。此外,我们还表明,在冬眠过程中,有丝分裂原激活的蛋白激酶(MAPK)和蛋白磷酸酶 1 途径受到了迄今为止尚未报道的抑制。值得注意的是,冬眠仓鼠中 MAPK 抑制剂(双特异性磷酸酶和 sproutys)上调,MAPK 诱导的转录因子(TFs)水平降低。启动子甲基化被发现可以调节这些 TF 靶向基因的表达。总之,我们记录了冬眠阶段之间的基因调控,这可能有助于确定途径和靶点,以防止移植或缺血再灌注中的器官损伤。