• Chao Ren, Yuyang Liu, Zhangna Ding, Zhanyu Yang, Tao Wan, Ning Zhang, Junyi Chen, Hui Feng, and Qi Liu.
• Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
• Shock. 2024 Nov 29.

BackgroundSepsis is a life-threatening condition driven by a dysregulated immune response to infection. Identifying the genetic factors underlying sepsis pathogenesis remains a major challenge in developing effective treatments.MethodsThe Summary-data-based Mendelian Randomization method was used to integrate genome-wide association study and expression quantitative trait loci data to identify sepsis-related genes. These genes were intersected with prognostic gene sets from Gene Expression Omnibus transcriptomic datasets and validated using an independent dataset. Comprehensive single-cell RNA sequencing analysis, including cell clustering, differential expression analysis, cell-cell communication mapping, and pseudotime trajectory analysis, was performed to explore the roles of the identified genes within the sepsis microenvironment.ResultsIntersection of Summary-data-based Mendelian Randomization and Gene Expression Omnibus gene sets, followed by validation, identified two risk genes and five protective genes as significantly differentially expressed. The risk gene BEND7, predominantly expressed in platelets, was further analyzed using single-cell RNA sequencing, revealing strong interactions with immune cells, particularly monocytes and neutrophils, via the intercellular adhesion molecule signaling pathway. Functional enrichment analysis suggested that BEND7-positive platelets play a role in immune modulation and platelet activation.ConclusionBEND7 was identified as a platelet-specific gene involved in immune regulation during sepsis. Targeting BEND7-positive platelets may present new therapeutic opportunities in sepsis management.Copyright © 2024 by the Shock Society.

12 keywords...

hide…