Abstract:
:The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Exo-S, 60-80 nm) and discovered an abundant population of non-membranous nanoparticles termed 'exomeres' (~35 nm). Exomere proteomic profiling revealed an enrichment in metabolic enzymes and hypoxia, microtubule and coagulation proteins as well as specific pathways, such as glycolysis and mTOR signalling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signalling pathways, respectively. Exo-S, Exo-L and exomeres each had unique N-glycosylation, protein, lipid, DNA and RNA profiles and biophysical properties. These three nanoparticle subsets demonstrated diverse organ biodistribution patterns, suggesting distinct biological functions. This study demonstrates that AF4 can serve as an improved analytical tool for isolating extracellular vesicles and addressing the complexities of heterogeneous nanoparticle subpopulations.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Zhang H,Freitas D,Kim HS,Fabijanic K,Li Z,Chen H,Mark MT,Molina H,Martin AB,Bojmar L,Fang J,Rampersaud S,Hoshino A,Matei I,Kenific CM,Nakajima M,Mutvei AP,Sansone P,Buehring W,Wang H,Jimenez JP,Cohen-Gould L,Pdoi
10.1038/s41556-018-0040-4subject
Has Abstractpub_date
2018-03-01 00:00:00pages
332-343issue
3eissn
1465-7392issn
1476-4679pii
10.1038/s41556-018-0040-4journal_volume
20pub_type
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