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Dev Cell. 2019 Feb 25;48(4):573-589.e4. doi: 10.1016/j.devcel.2019.01.004. Epub 2019 Feb 7.

Live Tracking of Inter-organ Communication by Endogenous Exosomes In Vivo.

Author information

1
Institut Curie, PSL Research University, CNRS UMR144, Paris 75005, France; Institute for Psychiatry and Neuroscience Paris, Hopital Saint-Anne, Université Descartes, INSERM U894, Paris 75014, France. Electronic address: frederik.verweij@inserm.fr.
2
Institut Curie, PSL Research University, INSERM U934, CNRS UMR3215, Sorbonne Université, Paris 75005, France.
3
Institut Curie, PSL Research University, Centre de Recherche, Laboratoire de Spectrométrie de Masse Protéomique, Paris, France.
4
Department of Pathology, Cancer Center Amsterdam, the Netherlands.
5
INSERM UMR_S1109, Université de Strasbourg, Fédération de Médecine Translationnelle de Strasbourg, Strasbourg, France.
6
Centre de Recherche en Cancérologie de Marseille, Aix-Marseille Université, Marseille 13284, France.
7
Institut Pasteur, Department of Developmental & Stem Cell Biology, 25 rue du Dr Roux, Paris 75015, France.
8
Institut Curie, PSL Research University, CNRS UMR144, Paris 75005, France.
9
Institut Curie, PSL Research University, CNRS UMR144, Paris 75005, France; Institute for Psychiatry and Neuroscience Paris, Hopital Saint-Anne, Université Descartes, INSERM U894, Paris 75014, France. Electronic address: guillaume.van-niel@inserm.fr.

Abstract

Extracellular vesicles (EVs) are released by most cell types but providing evidence for their physiological relevance remains challenging due to a lack of appropriate model organisms. Here, we developed an in vivo model to study EV function by expressing CD63-pHluorin in zebrafish embryos. A combination of imaging methods and proteomic analysis allowed us to study biogenesis, composition, transfer, uptake, and fate of individual endogenous EVs. We identified a subpopulation of EVs with exosome features, released in a syntenin-dependent manner from the yolk syncytial layer into the blood circulation. These exosomes are captured, endocytosed, and degraded by patrolling macrophages and endothelial cells in the caudal vein plexus (CVP) in a scavenger receptor- and dynamin-dependent manner. Interference with exosome biogenesis affected CVP growth, suggesting a role in trophic support. Altogether, our work represents a system for studying endogenous EV function in vivo with high spatiotemporal accuracy, demonstrating functional inter-organ communication by exosomes.

KEYWORDS:

CD63-pHluorin; exosome internalization; exosomes; extracellular vesicles; in situ electron microscopy; live-tracking; macrophages; scavenger endothelial cells; yolk syncytial layer; zebrafish

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