ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1607732
Single-cell transcriptomic and m6A methylation analyses reveal platelet-mediated immune regulatory mechanisms in sepsis
Provisionally accepted- 1Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
- 2Medical Records and Statistics Department, Tianjin Medical University General Hospital, Tianjin, China
- 3Department of Immunology, International Cancer Center, Shenzhen University Health Science Center, Shenzhen, China
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Sepsis is a life-threatening syndrome characterized by a dysregulated host response to infection and systemic inflammation, with a highly heterogeneous and complex immunopathology. Immune imbalance plays a central role in its progression. In recent years, the immunomodulatory functions of platelets have garnered increasing attention, revealing roles beyond their classical functions in hemostasis and thrombosis. Concurrently, N6-methyladenosine (m6A)-the most prevalent internal modification in eukaryotic mRNA-has been implicated in the regulation of immune responses and cell fate decisions. However, its role in sepsis remains poorly understood. In this study, we integrated single-cell RNA sequencing (scRNA-seq) data from the GSE167363 dataset and m6A methylome profiles of peripheral blood mononuclear cells (PBMCs) from sepsis patients. Then, a comprehensive analysis of immune cell composition, developmental trajectories, intercellular communication, and epigenetic modifications across healthy controls, survivors, and non-survivors was conducted. Our findings revealed a progressive enrichment of platelets during sepsis progression, along with a potential phenotypic reprogramming of B cells, T cells, and Tregs toward platelet-like characteristics.Cell-cell communication analysis showed an overall weakening of immune cell interactions with disease severity, most notably a marked attenuation of the APP-CD74 signaling axis between platelets and B cells, suggesting impaired immune network coordination. m6A profiling further revealed the remodeling of m6A peaks and dysregulation of m6A-related enzymes in the nonsurvivor group. Through integrative analysis, we identified RPA1 as a key m6A-modified target gene highly correlated with APP expression and under the co-regulation of multiple m6A regulators.Collectively, our study uncovers disrupted immune cell communication, functional reprogramming of platelets, and a potential m6A-dependent regulatory mechanism in sepsis. These findings provide
Keywords: Sepsis, Single-cell transcriptomics, m6A methylation, platelets, RPA1, APP-CD74 signaling axis
Received: 09 Apr 2025; Accepted: 02 Jun 2025.
Copyright: © 2025 Qian, Liu, Zhao, Dong, Jian and Shou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Songtao Shou, Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin, China
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