Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.
Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.
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DOI：
10.1038/s41556-018-0040-4
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发表时间：
2018-03
影响因子：
21.3
通讯作者：
Lyden D
中科院分区：
文献类型：
--
作者：
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;Paknejad N;Brendel M;Manova-Todorova K;Magalhães A;Ferreira JA;Osório H;Silva AM;Massey A;Cubillos-Ruiz JR;Galletti G;Giannakakou P;Cuervo AM;Blenis J;Schwartz R;Brady MS;Peinado H;Bromberg J;Matsui H;Reis CA;Lyden D
外体种群的异质性阻碍了我们对其生物发生、分子组成、生物分布和功能的理解。利用非对称流场流分离技术，我们鉴定了两个外体亚群(大的外体小泡，Exo-L，90-120 nm；小的外体小泡，Exo-S，60-80 nm)，并发现了丰富的非膜性纳米粒子群，称为“外小体”(~35 nm)。Exomere蛋白质组图谱显示，代谢酶和缺氧、微管和凝血蛋白以及特定的途径，如糖酵解和mTOR信号转导途径丰富。外源S和外源L分别含有与内体功能和分泌途径、有丝分裂纺锤体和IL-2/STAT5信号通路有关的蛋白质。外源S、外源L和外显子均具有独特的N-糖基化、蛋白质、脂肪、核酸和生物物理性质。这三个纳米粒子亚群显示了不同的器官生物分布模式，表明了不同的生物功能。这项研究表明，AF4可以作为一种改进的分析工具，用于分离和解决不同纳米粒子亚群的复杂性。
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 and specific pathways, such as glycolysis and mTOR signaling. Exo-S and Exo-L contained proteins involved in endosomal function and secretion pathways, and mitotic spindle and IL-2/STAT5 signaling pathways, respectively. Exo-S, Exo-L, and exomeres each had unique N-glycosylation, protein, lipid, and 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 and addressing the complexities of heterogeneous nanoparticle subpopulations.
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DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
16
作者：
Gardiner C;Harrison P;Belting M;Böing A;Campello E;Carter BS;Collier ME;Coumans F;Ettelaie C;van Es N;Hochberg FH;Mackman N;Rennert RC;Thaler J;Rak J;Nieuwland R
通讯作者：
Nieuwland R
影响因子：
56.9
作者：
Golub, TR;Slonim, DK;Lander, ES
通讯作者：
Lander, ES
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
影响因子：
14.8
作者：
Jensen, Pia H.;Karlsson, Niclas G.;Packer, Nicolle H.
通讯作者：
Packer, Nicolle H.