Small RNA sequencing in cells and exosomes identifies eQTLs and 14q32 as a region of active export

Exosomes are small extracellular vesicles that carry heterogeneous cargo, including RNA, between cells. Increasing evidence suggests that exosomes are important mediators of intercellular communication and biomarkers of disease. Despite this, the variability of exosomal RNA between individuals has not been well quantified. To assess this variability, we sequenced the small RNA of cells and exosomes from a 17-member family. Across individuals, we show that selective export of miRNAs occurs not only at the level of specific transcripts, but that a cluster of 74 mature miRNAs on chromosome 14q32 is massively exported in exosomes while mostly absent from cells. We also observe more inter-individual variability between exosomal samples than between cellular ones and identify four miRNA expression quantitative trait loci (eQTLs) shared between cells and exosomes. Our findings indicate that genomically co-located miRNAs can be exported together and highlight the variability in exosomal miRNA levels between individuals as relevant for exosome use as diagnostics. Small RNA-Sequencing of CEPH/UTAH family 1463 cells and exosomes