Jha Pawan K, Valekunja Utham K, Reddy Akhilesh B
Department of Systems Pharmacology & Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Sci Rep. 2025 Jul 29;15(1):27677. doi: 10.1038/s41598-025-10783-8.
Sleep regulation follows a homeostatic pattern. The mammalian cerebral cortex is the repository of homeostatic sleep drive and neurons and astrocytes of the cortex are principal responders of sleep need. The molecular mechanisms by which these two cell types respond to sleep loss are not yet clearly understood. By combining cell-type specific transcriptomics and nuclear proteomics we investigated how sleep loss affects the cellular composition and molecular profiles of these two cell types in a focused approach. The results indicate that sleep deprivation regulates gene expression and nuclear protein abundance in a cell-type-specific manner. Our integrated multi-omics analysis suggests that this distinction arises because neurons and astrocytes employ different gene regulatory strategies under accumulated sleep pressure. These findings provide a comprehensive view of the effects of sleep deprivation on gene regulation in neurons and astrocytes.
睡眠调节遵循一种稳态模式。哺乳动物的大脑皮层是稳态睡眠驱动力的储存库，皮层中的神经元和星形胶质细胞是睡眠需求的主要响应者。这两种细胞类型对睡眠缺失做出反应的分子机制尚未完全清楚。通过结合细胞类型特异性转录组学和细胞核蛋白质组学，我们以一种聚焦的方式研究了睡眠缺失如何影响这两种细胞类型的细胞组成和分子特征。结果表明，睡眠剥夺以细胞类型特异性的方式调节基因表达和细胞核蛋白丰度。我们的综合多组学分析表明，这种差异的出现是因为神经元和星形胶质细胞在累积的睡眠压力下采用了不同的基因调控策略。这些发现提供了关于睡眠剥夺对神经元和星形胶质细胞基因调控影响的全面观点。
