{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T14:42:52Z","timestamp":1782139372200,"version":"3.54.5"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>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 N\u2076-methyladenosine (m<jats:sup>6<\/jats:sup>A) modification in sepsis, with a particular focus on the functional remodeling of platelets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study integrated single-cell RNA sequencing data (GSE167363 dataset) from sepsis patients with m<jats:sup>6<\/jats:sup>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<jats:sup>6<\/jats:sup>A modifications among healthy controls, survivors, and non-survivors, and further screened for key m<jats:sup>6<\/jats:sup>A-regulated target genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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\u2013cell communication analysis showed a marked decline in communication strength among immune cells as the disease worsened, particularly a significant weakening of the APP\u2013CD74 signaling pathway between platelets and B cells, indicating impaired immune network synergy. m\u2076A methylation sequencing revealed distinct remodeling of m\u2076A peaks and dysregulation of related regulatory factors in non-survivors. Further integrative analysis identified RPA1 as a key m\u2076A-regulated target gene, whose expression was closely associated with APP and co-regulated by multiple m<jats:sup>6<\/jats:sup>A-modifying factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reveals disruptions in immune cell interactions and an m<jats:sup>6<\/jats:sup>A-dependent mechanism of platelet functional remodeling during sepsis progression. The identification of the key target gene RPA1 offers new insights into the immunopathological mechanisms of sepsis and lays a theoretical foundation for future precision interventions and therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1607732","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T05:21:37Z","timestamp":1750656097000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Single-cell transcriptomic and m6A methylation analyses reveal platelet-mediated immune regulatory mechanisms in 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