title: Small RNA Sequencing in Cells and Exosomes Identifies eQTLs and 14q32 as a Region of Active Export.
abstract: 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 interindividual variability between exosomal samples than between cellular ones and identify four miRNA expression quantitative trait loci shared between cells and exosomes. Our findings indicate that genomically colocated miRNAs can be exported together and highlight the variability in exosomal miRNA levels between individuals as relevant for exosome use as diagnostics.
authors: Biomedical Informatics Program, Stanford University, California 94305.|Department of Pathology, Stanford University, California 94305.
authors: Emily K
authors: EK
authors: Tsang
authors: Department of Pathology, Stanford University, California 94305.|Department of Genetics, Stanford University, California 94305.
authors: Nathan S
authors: NS
authors: Abell
authors: Department of Pathology, Stanford University, California 94305.
authors: Xin
authors: X
authors: Li
authors: Department of Pathology, Stanford University, California 94305.
authors: Vanessa
authors: V
authors: Anaya
authors: Biomedical Informatics Program, Stanford University, California 94305.
authors: Konrad J
authors: KJ
authors: Karczewski
authors: Department of Genetics, Stanford University, California 94305.|Department of Radiology, Stanford University, California 94305.
authors: David A
authors: DA
authors: Knowles
authors: Stanford PULSE Institute, SLAC National Accelerator Lab, Menlo Park, California 94025.
authors: Raymond G
authors: RG
authors: Sierra
authors: Department of Pathology, Stanford University, California 94305.
authors: Kevin S
authors: KS
authors: Smith
authors: Department of Pathology, Stanford University, California 94305 smontgom@stanford.edu.|Department of Genetics, Stanford University, California 94305.
authors: Stephen B
authors: SB
authors: Montgomery
mesh_terms: D002460:Cell Line; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D055354:Exosomes / Q000235:genetics*; D005786:Gene Expression Regulation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering
keywords: extracellular vesicles; gene regulation; miRNA; piRNA