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Séminaire impromptu - Guillaume van NielLive tracking of exosome secretion and communication

Abstract :


 Exosomes are a nano-sized subclass of Extracellular Vesicles (EVs), released by a wide variety of cell types, that have been implicated in many important physiological and pathological processes.
Despite of their promising use as biomarkers and drug vehicles, very little is known about the dynamic of their secretion and their physiology in vivo.

Here we proposed to fill this gap by developing a hCD63-based fluorescent reporter that allowed us to follow their secretion in live cells and to follow endogenous exosomes 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 (LM and EM) 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. 

As a unique window into the behavior of endogenous EVs in the complex tissue architecture of vertebrates, this model will open new avenues to unravel fundamental aspects in EV biology and will aid to exploit the full potential of EVs as biomarkers and drug vehicles.