Abstract

Live Tracking of Endogenous Exosomes in vivo

Guillaume Van Niel, Research Scientist, Institute Curie

Despite of their promising use as biomarkers and drug vehicles, very little is known about the dynamic of extracellular vesicles (EVs) secretion and their physiology in vivo. Here we proposed to fill this gap by developing a hCD63-based fluorescent reporter that allowed us to analyze their secretion in live cells and to track them from their site of production to their final destination in in vivo models. The use of this construct in cell lines revealed specific features and new stimulatory pathway of exosome secretion. The use of this construct in zebrafish embryos allowed us to observe exosome release in vivo and track a massive pool of endogenous exosomes in the blood flow by combining light- and electron microscopy techniques. After cell specific expression of the construct in vivo, we tracked endogenous exosomes by live imaging in the blood flow to identify their main targets. The mapping of the transit routes and final destination of EVs in zebrafish embryos support their role in nutrient delivery during development. Altogether, our work highlights the use of fluorescent reporter to study the regulation of exosome secretion and the use of the zebrafish embryo as a relevant vertebrate model to track endogenous EVs in vivo.