The nematode Caenorhabditis elegans has been instrumental in the identification of evolutionarily conserved mechanisms of aging. C. elegans also has recently been found to have evolutionarily conserved extracellular vesicle (EV) signaling pathways. We have been developing tools that allow for the detailed study of EV biology in C. elegans. Here we apply our recently published method for high specificity purification of EVs from C. elegans to carry out target-independent proteomic and RNA analysis of nematode EVs. We identify diverse coding and non-coding RNA and protein cargo types commonly found in human EVs. The EV cargo spectrum is distinct from whole worms, suggesting that protein and RNA cargos are actively recruited to EVs. Gene ontology analysis revealed C. elegans EVs are enriched for extracellular-associated and signaling proteins, and network analysis indicates enrichment for metabolic, immune, and basement membrane associated proteins. Tissue enrichment and gene expression analysis suggests the secreted EV proteins are likely to be derived from intestine, muscle, and excretory tissue. An unbiased comparison of the EV proteins with a large database of C. elegans genome-wide microarray data showed significant overlap with gene sets that are associated with aging and immunity. Taken together our data suggest C. elegans could be a promising in vivo model for studying the genetics and physiology of EVs in a variety of contexts including aging, metabolism, and immune response.

中文翻译：

---

秀丽隐杆线虫细胞外囊泡的组成表明在新陈代谢、免疫和衰老中的作用。

线虫秀丽隐杆线虫有助于鉴定进化上保守的衰老机制。最近还发现秀丽隐杆线虫具有进化上保守的细胞外囊泡 (EV) 信号通路。我们一直在开发工具，允许对秀丽隐杆线虫中的 EV 生物学进行详细研究。在这里，我们应用我们最近发表的方法从秀丽隐杆线虫中高特异性纯化 EV对线虫 EV 进行不依赖靶点的蛋白质组学和 RNA 分析。我们确定了人类 EV 中常见的多种编码和非编码 RNA 和蛋白质货物类型。EV 货物谱不同于整个蠕虫，这表明蛋白质和 RNA 货物被积极招募到 EV 中。基因本体分析显示，秀丽隐杆线虫EV 富含细胞外相关蛋白和信号蛋白，网络分析表明代谢、免疫和基底膜相关蛋白的富集。组织富集和基因表达分析表明，分泌的 EV 蛋白可能来源于肠道、肌肉和排泄组织。EV 蛋白与大型秀丽隐杆线虫数据库的无偏比较全基因组微阵列数据显示与衰老和免疫相关的基因组有显着重叠。综上所述，我们的数据表明，秀丽隐杆线虫可能是一种很有前途的体内模型，用于研究 EV 在各种环境中的遗传学和生理学，包括衰老、新陈代谢和免疫反应。