Cell‐Type‐Specific mRNA N 6 ‐Methyladenosine Landscape and Regulatory Mechanisms Underlying Immune Dysregulation of Sleep‐Deprived

作者：Yakun Liu, Zhe Wang, Sha Liu, Xinrong Li, Denggao Wang, Dan Wang, Ying Li, Chaojie Liu, Yong Xu · 发表于：Journal of Pineal Research · 年份：2025 · DOI：10.1111/jpi.70046 · 被引用次数：4 · 研究领域：Epigenetics and DNA Methylation、Immune Cell Function and Interaction、RNA modifications and cancer

ABSTRACT Sleep deprivation impairs daytime cognitive functioning and is a risk factor for various diseases related to immune dysregulation. N 6 ‐methyladenosine (m 6 A) is a common epigenetic RNA modification with essential roles in regulating neurogenesis and circadian rhythms. m 6 A dysregulation resulting in immune imbalance has received much attention. In this study, we elucidated the landscape and specific mechanisms of m 6 A regulators in the peripheral blood of patients with sleep deprivation through RNA sequencing and single‐cell transcriptomics data sets. We observed that m 6 A regulator upregulation aggravated sleep loss and immune disorders. Women were more sensitive to sleep deprivation. Notably, m 6 A regulator ALKBH5 was downregulated in peripheral blood mononuclear cells (PBMC) of patients with sleep deprivation at the transcriptome level. However, ALKBH5 was cell‐type specific upregulated in T cells (TC), B cells (BC), and natural killer (NK) cells, involving the dysregulation of acquired immune mechanisms by aberrant cell–cell communication that mediated ligand–receptor interactions across diverse cell types. Furthermore, the immune dysregulation of sleep loss could be regulated by a potential pathway between ALKBH5 and CD99 in SH‐SY5Y and HT22 cells. Sleep deprivation group CD3 + /CD45 + T cells had higher levels of ALKBH5 mRNA than the control group. This study demonstrated that abnormal m 6 A modification patterns caused by m 6 A regulators play a key role...