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Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation

 Haiying Zhang  ;  Daniela Freitas  ;  Han Sang Kim  ;  Kristina Fabijanic  ;  Zhong Li  ;  Haiyan Chen  ;  Milica Tesic Mark  ;  Henrik Molina  ;  Alberto Benito Martin  ;  Linda Bojmar  ;  Justin Fang  ;  Sham Rampersaud  ;  Ayuko Hoshino  ;  Irina Matei  ;  Candia M. Kenific  ;  Miho Nakajima  ;  Anders Peter Mutvei  ;  Pasquale Sansone  ;  Weston Buehring  ;  Huajuan Wang  ;  Juan Pablo Jimenez  ;  Leona Cohen-Gould  ;  Navid Paknejad  ;  Matthew Brendel  ;  Katia Manova-Todorova  ;  Ana Magalhães  ;  José Alexandre Ferreira  ;  Hugo Osório  ;  André M. Silva  ;  Ashish Massey  ;  Juan R. Cubillos-Ruiz  ;  Giuseppe Galletti  ;  Paraskevi Giannakakou  ;  Ana Maria Cuervo  ;  John Blenis  ;  Robert Schwartz  ;  Mary Sue Brady  ;  Héctor Peinado  ;  Jacqueline Bromberg  ;  Hiroshi Matsui  ;  Celso A. Reis  ;  David Lyden 
 NATURE CELL BIOLOGY, Vol.20(3) : 332-343, 2018 
Journal Title
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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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Han Sang(김한상) ORCID logo https://orcid.org/0000-0002-6504-9927
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