The extracellular vesicle transcriptome provides tissue-specific functional genomic annotation relevant to disease susceptibility in obesity

作者：Emeli Chatterjee, Michael J. Betti, Quanhu Sheng, Phillip Lin, Margo P. Emont, Guoping Li, Kaushik Amancherla, Marta García-Contreras, Priyanka Gokulnath, Worawan B. Limpitikul, Olivia Rosina Whittaker, Kathy Luong, Christopher Azzam, Denise W. Gee, Matthew Hutter, Karen Flanders, Parul Sahu, Charles R. Flynn, Jonathan D. Brown, Danxia Yu, Evan D. Rosen, Kendall Jensen, Eric R. Gamazon, Ravi V. Shah, Saumya Das · 发表于：Cell Genomics · 年份：2025 · DOI：10.1016/j.xgen.2025.100925 · 被引用次数：6 · 研究领域：RNA modifications and cancer、Adipokines, Inflammation, and Metabolic Diseases、Extracellular vesicles in disease

We characterized circulating extracellular vesicles (EVs) in obese and lean humans, identifying transcriptional cargo differentially expressed in obesity (277 unique genes; false discovery rate < 10%). Since circulating EVs may have broad origin, we compared this obesity EV transcriptome with expression from human visceral-adipose-tissue-derived EVs from freshly collected and cultured biopsies from the same obese individuals, observing high concordance. Using a comprehensive set of adipose-specific epigenomic and chromatin conformation assays, we found that the differentially expressed transcripts from the EVs were those regulated in adipose by body mass index-associated SNPs ( p < 5 × 10 − 8) from a large-scale genome-wide association study (GWAS). Using a phenome-wide association study of the regulatory SNPs for the EV-derived transcripts, we identified a substantial enrichment for inflammatory phenotypes, including type 2 diabetes. Collectively, these findings represent the convergence of the GWAS (genetics), epigenomics (transcript regulation), and EV (liquid biopsy) fields, enabling powerful future genomic studies of complex diseases.