Table 2_Multiple time points of transcriptome analysis revealed altered genes involved in maintaining hibernation in the hypothalamus of Tamias sibiricus.csv

Hibernation, an adaptive mechanism to extreme environmental conditions, is prevalent among mammals. Its main characteristics include reduced body temperature and metabolic rate. However, the mechanisms by which hibernating animals re-enter deep sleep during the euthermic phase to sustain hibernation remain poorly understood. We selected the Tamias sibiricus as a model organism and conducted transcriptomic sequencing of its hypothalamus at multiple time points throughout hibernation. Through the strategies of gene set filtering and intersection analysis, we effectively filtered out redundant data, identifying a subset of genes whose expression was downregulated during the euthermic phase potentially inducing re-enter deep sleep, thereby maintaining the periodic cycles of torpor and arousal. These cycles are crucial for sustaining the overall hibernation process. Notably, genes associated with sodium and potassium ion channels were significantly enriched. Specifically, potassium ion-related genes such as Kcnc1, Kcna2, Kcng4, and Kcna6, along with sodium ion-related genes such as Scn1a and Hcn2, were markedly downregulated. qRT-PCR validation of four of these genes (Kcnc1, Kcna6, Scn1a, and Hcn2) confirmed significant downregulation during the euthermic phase compared to the deep sleep phase, further supporting our transcriptomic findings. This study provides novel insights into the hypothalamic transcriptome dynamics at various hibernation stages. Although the functional roles of these genes require further investigation, our findings lay the groundwork for future studies to elucidate the molecular mechanisms underlying hibernation.

冬眠是哺乳动物应对极端环境的适应性机制，在哺乳动物中广泛存在。其核心特征为体温降低与代谢速率放缓。然而，冬眠动物如何在温相阶段（euthermic phase）重新进入深度睡眠以维持冬眠状态，其背后的调控机制仍未被充分阐明。本研究选取西伯利亚花栗鼠（Tamias sibiricus）作为模式生物，对其整个冬眠周期内多个时间点的下丘脑组织开展了转录组测序。通过基因集筛选与交集分析策略，我们有效剔除了冗余数据，筛选出一批在温相阶段表达下调的基因；这类基因或可诱导动物重新进入深度睡眠，进而维持蛰伏与觉醒的周期性循环。该周期性循环对维持整体冬眠过程至关重要。值得注意的是，与钠、钾离子通道相关的基因在该基因集中显著富集。具体而言，钾离子相关基因如Kcnc1、Kcna2、Kcng4及Kcna6，以及钠离子相关基因如Scn1a与Hcn2，均呈现显著下调表达。本研究对其中4个基因（Kcnc1、Kcna6、Scn1a及Hcn2）进行了qRT-PCR验证，结果证实相较于深度睡眠阶段，这些基因在温相阶段的表达量显著下调，进一步佐证了转录组测序的分析结果。本研究为解析不同冬眠阶段下下丘脑的转录组动态变化提供了全新视角。尽管这些基因的具体功能仍有待进一步探究，但本研究结果为未来阐明冬眠的分子调控机制奠定了重要基础。