High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources.
High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources.
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DOI：
10.3402/jev.v5.32570
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发表时间：
2016
影响因子：
16
通讯作者：
Khvorova A
中科院分区：
文献类型：
--
作者：
Haraszti RA;Didiot MC;Sapp E;Leszyk J;Shaffer SA;Rockwell HE;Gao F;Narain NR;DiFiglia M;Kiebish MA;Aronin N;Khvorova A
探索细胞外囊泡（EV），包括外来体和微囊泡（MV），用于诊断、治疗和药物递送。然而，很少有人知道的蛋白质和脂质组成的EV及其源细胞的关系。在这里，我们报告了高分辨率的脂质组学和蛋白质组学分析的外来体和MV来自3种不同的细胞类型：U87胶质母细胞瘤细胞，Huh 7肝细胞癌细胞和人骨髓间充质干细胞（MSC）的差异ultracentravation。我们在筛选中鉴定了3，532种蛋白质和1，961种脂质。外来体与MV在几个不同的领域不同：（a）外来体的蛋白质模式比MV的蛋白质模式更可能与其来源的细胞不同;（B）U87和Huh 7外泌体的蛋白质组彼此相似但不同于MSC外泌体的蛋白质组，而Huh 7和MSC外泌体的脂质体彼此相似，但与U87外泌体的脂质体不同;（c）外泌体具有细胞外基质、肝素结合、受体、免疫应答和细胞粘附功能的蛋白质，而MV富含内质网、蛋白酶体和线粒体蛋白。外泌体和MV的脂质含量类型也不同。糖脂和游离脂肪酸的富集表征了外来体，而神经酰胺和鞘磷脂的富集表征了MV。此外，Huh 7和MSC外泌体特异性地富含心磷脂; U87外泌体富含鞘磷脂。本研究全面分析了3种不同细胞类型中外来体、MV和源细胞的蛋白质和脂质组成。
Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), are explored for use in diagnostics, therapeutics and drug delivery. However, little is known about the relationship of protein and lipid composition of EVs and their source cells. Here, we report high-resolution lipidomic and proteomic analyses of exosomes and MVs derived by differential ultracentrifugation from 3 different cell types: U87 glioblastoma cells, Huh7 hepatocellular carcinoma cells and human bone marrow-derived mesenchymal stem cells (MSCs). We identified 3,532 proteins and 1,961 lipid species in the screen. Exosomes differed from MVs in several different areas: (a) The protein patterns of exosomes were more likely different from their cells of origin than were the protein patterns of MVs; (b) The proteomes of U87 and Huh7 exosomes were similar to each other but different from the proteomes of MSC exosomes, whereas the lipidomes of Huh7 and MSC exosomes were similar to each other but different from the lipidomes of U87 exosomes; (c) exosomes exhibited proteins of extracellular matrix, heparin-binding, receptors, immune response and cell adhesion functions, whereas MVs were enriched in endoplasmic reticulum, proteasome and mitochondrial proteins. Exosomes and MVs also differed in their types of lipid contents. Enrichment in glycolipids and free fatty acids characterized exosomes, whereas enrichment in ceramides and sphingomyelins characterized MVs. Furthermore, Huh7 and MSC exosomes were specifically enriched in cardiolipins; U87 exosomes were enriched in sphingomyelins. This study comprehensively analyses the protein and lipid composition of exosomes, MVs and source cells in 3 different cell types.
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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：
3.4
作者：
Kalra, Hina;Adda, Christopher G.;Mathivanan, Suresh
通讯作者：
Mathivanan, Suresh
影响因子：
16.6
作者：
Lai, Charles P.;Kim, Edward Y.;Badr, Christian E.;Weissleder, Ralph;Mempel, Thorsten R.;Tannous, Bakhos A.;Breakefield, Xandra O.
通讯作者：
Breakefield, Xandra O.
影响因子：
3.7
作者：
Duijvesz D;Burnum-Johnson KE;Gritsenko MA;Hoogland AM;Vredenbregt-van den Berg MS;Willemsen R;Luider T;Paša-Tolić L;Jenster G
通讯作者：
Jenster G
影响因子：
4.6
作者：
Balaj L;Atai NA;Chen W;Mu D;Tannous BA;Breakefield XO;Skog J;Maguire CA
通讯作者：
Maguire CA