Single-cell transcriptomic and m6A methylation analyses reveal platelet-mediated immune regulatory mechanisms in sepsis

作者：Weiwei Qian, Yuanyuan Liu, Xinyang Zhao, Yuxin Dong, Jian Zhou, Songtao Shou · 发表于：Frontiers in Immunology · 年份：2025 · DOI：10.3389/fimmu.2025.1607732 · 被引用次数：5 · 研究领域：RNA modifications and cancer、Peptidase Inhibition and Analysis、Cancer-related gene regulation

Objective Sepsis is a systemic inflammatory response syndrome triggered by infection, characterized by high clinical heterogeneity and complex immunopathological mechanisms. Immune dysregulation plays a central role in its progression. This study aims to investigate the compositional changes of immune cells, characteristics of intercellular communication, and potential regulatory mechanisms of N⁶-methyladenosine (m 6 A) modification in sepsis, with a particular focus on the functional remodeling of platelets. Methods This study integrated single-cell RNA sequencing data (GSE167363 dataset) from sepsis patients with m 6 A methylation sequencing data of peripheral blood mononuclear cells (PBMCs). Through systematic analysis, we compared the differences in immune cell composition, developmental trajectories, intercellular communication, and m 6 A modifications among healthy controls, survivors, and non-survivors, and further screened for key m 6 A-regulated target genes. Results The analysis revealed that platelets gradually accumulated during the progression of sepsis, while B cells, T cells, and regulatory T cells (Tregs) exhibited a trend toward platelet-like phenotypic remodeling. Cell–cell communication analysis showed a marked decline in communication strength among immune cells as the disease worsened, particularly a significant weakening of the APP–CD74 signaling pathway between platelets and B cells, indicating impaired immune network synergy. m⁶A methylation sequencing...