Tracking extracellular vesicle (EV) cargo as a platform for studying EVomics, signaling, and targeting in vivo.

Nikonorova IA, Wang J, Cope AL, Tilton PE, Power KM, Walsh JD, Akella JS, Krauchunas AR, Shah P, Barr MM.

bioRxiv : 10.1101/2021.09.23.461577

2021

Download
PDF
DOI
Source code
# Abstract Extracellular vesicle (EV)-based signaling is a challenge to study, due to EV small size, heterogeneity, and limited information on cargo content in vivo. We present Caenorhabditis elegans as a discovery platform that allows single EV tracking from source to target tissue in living animals. We enriched ciliary EVs using GFP-tagged PKD-2 cargo followed by mass spectrometry analysis to identify 2,888 cargo candidates. By integrating our dataset with single-cell transcriptomic data, we identified EV cargo produced by individual neurons and other cell and tissue types. A single cilium produces multiple EVs with distinct protein content. Ciliary EVs carry nucleic acid binding proteins. We observed transfer of EV cargo from the male reproductive tract to the hermaphrodite uterus during mating, a direct demonstration of animal-to-animal EV targeting.