Quantitative Proteomics Identifies Sytenin-1 as a Universal Biomarker of Exosomes

Exosomes are extracellular vesicles derived from the endosomal compartment. They contain a multitude of bioactive constituents and mediate intercellular communication in health and disease. The frequently used biomarkers of exosomes are heterogeneous and do not exhibit universal utility across different cell types. To uncover ubiquitous and abundant proteins that can serve as universal biomarkers of exosomes, we employed an unbiased and quantitative proteomic approach based on Super SILAC coupled to high-resolution mass spectrometry (MS). In total 1,243 proteins were consistently quantified in the proteome of exosomes, irrespective of the cellular source or isolation method. Among them, a cohort of 22 proteins were universally enriched, and 15 proteins consistently depleted in the proteome of exosomes when compared to cells. Among the enriched proteins, we found several membrane proteins and GTPases, whereas the cohort of depleted proteins was predominantly composed by nuclear proteins. Our study revealed that Syntenin-1 is the most abundant ubiquitous protein in exosomes from distinct cell sources, thus representing an ideal candidate for universal biomarker of exosomes.

外泌体（Exosomes）是源自内体区室的细胞外囊泡，携带有多种生物活性成分，在生理与病理状态下均介导细胞间通讯。当前常用的外泌体生物标志物存在异质性，且无法在不同细胞类型中实现通用应用。为挖掘可作为外泌体通用生物标志物的普适性高丰度蛋白，本研究采用基于Super SILAC（超稳定同位素标记细胞培养）耦合高分辨率质谱（MS）的无偏倚定量蛋白质组学方法。无论细胞来源或外泌体分离方法如何，本研究均在外泌体蛋白质组中稳定定量到1243种蛋白。其中，与亲本细胞相比，22种蛋白在所有外泌体中均普遍富集，另有15种蛋白持续缺失；富集蛋白中包含多种膜蛋白与GTP酶，而缺失蛋白则主要由核蛋白构成。本研究发现，Syntenin-1（黏着斑蛋白-1）是不同细胞来源外泌体中丰度最高的普适性蛋白，因此是理想的外泌体通用生物标志物候选分子。