Pluto Bioinformatics

GSE87290: RNA-seq of human peripheral blood mononuclear cells

Bulk RNA sequencing

Inflammatory cytokine responses to activation of innate immunity differ between individuals, yet the genomic and transcriptomic determinants of inflammatory responsiveness are not well understood. We hypothesized that mRNA and lincRNA expression is modulated in disease-relevant tissues in humans in vivo during inflammation, and differs between individuals with divergent evoked inflammatory responses. In the Genetics of Evoked Response to Niacin and Endotoxemia (GENE) Study, we performed an inpatient endotoxin challenge (1ng/kg LPS) in healthy humans. We selected individuals in the top (high-responders) and bottom (low-responders) extremes for inflammatory responses, and applied RNASeq to peripheral blood mononuclear cells (PBMC, n=15) before and after LPS administration. At baseline, there were limited differences in gene expression by sex or race. Further, only a small number of genes differed between high and low responders at baseline. Post-LPS, there were clear differences in the magnitude of the transcriptional response between high and low responders, with a far greater number of genes differentially expressed post-LPS in high responders, consistent with the clinical response. We also found a number of differentially expressed long intergenic non-coding RNAs (lincRNAs) post-LPS. We show that differences in gene expression may drive differences in clinical inflammatory response, and that differentially expressed genes and lincRNAs represent novel candidates for modulation of immune and metabolic responses in acute and chronic diseases. SOURCE: Chenyi Xue Columbia University