Journal
CELL REPORTS
Volume 27, Issue 3, Pages 940-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.01.009
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Funding
- NIH Common Fund's ex-RNA Communication Program
- NIH [R01 GM111093]
- NCI [P50 CA095103, R35 CA197570, U19 CA179514, R01CA163563, R01 CA046413]
- Vanderbilt-Ingram Cancer Center [P30 CA68485]
- Vanderbilt Digestive Disease Research Center [P30 DK058404]
- Vanderbilt Cell Imaging Shared Resource
- Vanderbilt Technologies for Advanced Genomics Shared Resource
- Welborn Memorial Fund
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Exomeres are a recently discovered type of extracellular nanoparticle with no known biological function. Herein, we describe a simple ultracentrifugation-based method for separation of exomeres from exosomes. Exomeres are enriched in Argonaute 1-3 and amyloid precursor protein. We identify distinct functions of exomeres mediated by two of their cargo, the beta-galactoside alpha 2,6-sialyltransferase 1 W(ST6Gal-I) that alpha 2,6-sialylates N-glycans, and the EGFR ligand, amphiregulin (AREG). Functional ST6Gal-I in exomeres can be transferred to cells, resulting in hypersialylation of recipient cell-surface proteins including beta 1-integrin. AREG-containing exomeres elicit prolonged EGFR and downstream signaling in recipient cells, modulate EGFR trafficking in normal intestinal organoids, and dramatically enhance the growth of colonic tumor organoids. This study provides a simplified method of exomere isolation and demonstrates that exomeres contain and can transfer functional cargo. These findings underscore the heterogeneity of nanoparticles and should accelerate advances in determining the composition and biological functions of exomeres.
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