Characterization of Exogenous Sequence Fragments in Extracellular Vesicles from Human

Abstract

Extracellular vesicles (EVs) play crucial role in mediating intercellular communication. Small RNA is an important component in EVs. However, the proportion of small RNA sequencing (smRNA-seq) reads in EVs mapped to the human genome is much lower than that of cells, suggesting the existence of many nonhuman sequences in EVs. However, there is no systematic study on EV fragments unmapped to the human genome. Herein, using EV smRNA-seq data, the landscape of exogenous RNA cargoes in human EVs is portrayed. The results show the distribution of nonhuman sequence fragments in 1838 EV samples; an average of 21.82% of reads are unmapped to the human genome, and 12.33% are mapped to the collected exogenous reference sequences. Furthermore, the proportion of exogenous sequences in plasma EV samples is the lowest, while in the cell line EV samples, it is much higher, mainly from animals, bacteria, or contaminants. Exogenous sequences from plants are mainly from food, and the exogenous bacteria are mainly gut microbiota. Virus-derived sequences reflect the high prevalence of viruses in the population, such as herpesvirus and hepatitis virus. This study provides the first landscape of exogenous fragments in human EVs and implies diverse RNA sources in the human body.