Multi-organ Transcriptome Dynamics in a Mouse Model of Cecal Ligation and Puncture Induced Polymicrobial Sepsis

Purpose: During sepsis, an excessive inflammatory immune reaction contributes to multi-organ dys-function syndrome (MODS), a critical condition associated with high morbidity and mortality, however the molecular mechanisms driving MODS remain elusive. Methods: We used RNA sequencing to characterize transcriptional changes in the early phase of sepsis, at 6h, 12h, 24h time points, in lung, kidney, liver and heart tissues, in a cecal ligation and puncture (CLP) induced polymicrobial sepsis murine model. Results: The CLP surgery induced significant changes (adj. p-value <0.05) in expression of hundreds of transcripts in the four organs tested, with the highest number exceeding 2000 differentially expressed genes (DEGs) in all organs at 12h post-CLP. Over-representation analysis by functional annotations of DEGs to the Reactome database revealed the Immune system, Hemostasis, Lipid metabolism, Signal transduction and Extracellular matrix remodeling biological processes as significantly altered in at least two organs, while Metabolism of proteins and RNA as being liver tissue specific in the early phase of sepsis. Conclusion: RNA sequencing across organs and time-points in the CLP murine model allowed to study the trajectories of transcriptome changes demonstrating alterations common across multiple organs as well as biological pathways altered in an organ-specific manner. These findings could pave new directions in the research of sepsis-induced MODS and indicate new sepsis treatment strategies.