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oai:repisalud.isciii.es:20.500.12105/179732024-11-29T17:39:02Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Zhang, Haiying author Freitas, Daniela author Kim, Han Sang author Fabijanic, Kristina author Li, Zhong author Chen, Haiyan author Mark, Milica Tesic author Molina, Henrik author Martin, Alberto Benito author Bojmar, Linda author Fang, Justin author Rampersaud, Sham author Hoshino, Ayuko author Matei, Irina author Kenific, Candia M author Nakajima, Miho author Mutvei, Anders Peter author Sansone, Pasquale author Buehring, Weston author Wang, Huajuan author Jimenez, Juan Pablo author Cohen-Gould, Leona author Paknejad, Navid author Brendel, Matthew author Manova-Todorova, Katia author Magalhães, Ana author Ferreira, José Alexandre author Osório, Hugo author Silva, André M author Massey, Ashish author Cubillos-Ruiz, Juan R author Galletti, Giuseppe author Giannakakou, Paraskevi author Cuervo, Ana Maria author Blenis, John author Schwartz, Robert author Brady, Mary Sue author Peinado, Héctor author Bromberg, Jacqueline author Matsui, Hiroshi author Reis, Celso A author Lyden, David author 2018-03 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. Nat Cell Biol . 2018 ;20(3):332-343. 10.1038/s41556-018-0040-4 1476-4679 Nature cell biology https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931706/ 29459780 http://hdl.handle.net/20.500.12105/17973 Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.