Quantitative Biology / Gene Expression in Development & Disease Seminar

Friday, 25 January 2013 at 11:30am

Room 1400 Biomedical and Physical Sciences Bldg.

Refreshments at 11:15

Speaker:  Mingyao Li, Department of Biostatistics & Epidemiology, University of Pennsylvania School of Medicine

Title:  Translational Genomics Study in Evoked Human Inflammation

Inappropriate or sustained activation of innate immunity is a pathologic feature of several common cardiometabolic disorders. Little is known, however, about transcriptomic modulation during inflammatory stress in disease relevant human tissues. We applied RNA sequencing (RNA-Seq) during low-dose experimental endotoxemia (LPS) in healthy humans to interrogate, in an unbiased manner, inflammatory tissue level transcriptome responses of relevance to complex cardiometabolic diseases. We utilized adipose and blood samples from three healthy individuals who underwent a standardized inpatient endotoxemia protocol. Our comprehensive analysis revealed substantial, highly tissue-specific LPS modulated changes in the expression of protein-coding genes and lincRNAs as well as alternative splicing (AS). We also confirmed adipocytes and macrophages as potential cell sources of selective LPS modulated lincRNAs and AS events. We further defined disease relevance of a subset of findings in obese adipose tissue and through interrogation of overlap with genome-wide association study loci for cardiometabolic traits. Finally, we evaluated the relationship between RNA-Seq depth and the ability to detect differentially expressed (DE) genes and differential AS (DAS) events. Our results suggest that a much higher sequencing depth is needed to reliably identify DAS events than for DE genes. Our findings provide novel insights into tissue-level transcriptomic variations that are relevant to common cardiometabolic diseases.