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

Journal of Inflammation Research
Izabela RumienczykMichal Mikula

Abstract

During sepsis, an excessive inflammatory immune reaction contributes to multi-organ dysfunction syndrome (MODS), a critical condition associated with high morbidity and mortality; however, the molecular mechanisms driving MODS remain elusive. We used RNA sequencing to characterize transcriptional changes in the early phase of sepsis, at 6, 12, 24 hour time points in lung, kidney, liver, and heart tissues, in a cecal ligation and puncture (CLP)-induced polymicrobial sepsis murine model. 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 2,000 differentially expressed genes (DEGs) in all organs at 12 hours 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 were revelaed as being liver tissue specific in the early phase of sepsis. RNA sequencing across organs and time-points in the CLP murine model allowed us to study the trajectories of transcriptome ch...Continue Reading

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Software Mentioned

Ion Torrent RNASeqAnalysis Plugin
bowtie2
GraphGrid
R package ClusterProfiler
R package DESeq2
ComplexHeatmap R
Ensembl
Excel
Reactome
HTSeq

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