Department of Pathology, University of Washington, Seattle, WA, USA.
Institute for Systems Biology, Seattle, WA, USA.
Geroscience. 2020 Aug;42(4):1133-1145. doi: 10.1007/s11357-020-00204-1. Epub 2020 Jun 24.
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.
秀丽隐杆线虫在鉴定衰老过程中进化保守的机制方面发挥了重要作用。最近还发现，秀丽隐杆线虫具有进化保守的细胞外囊泡 (EV) 信号通路。我们一直在开发工具，以允许在秀丽隐杆线虫中对 EV 生物学进行详细研究。在这里，我们应用我们最近发表的从秀丽隐杆线虫中高特异性纯化 EV 的方法，对秀丽隐杆线虫 EV 进行无目标的蛋白质组学和 RNA 分析。我们鉴定出了在人类 EV 中常见的各种编码和非编码 RNA 和蛋白质货物类型。EV 货物谱与整个蠕虫不同，这表明蛋白质和 RNA 货物被主动募集到 EV 中。GO 分析显示，秀丽隐杆线虫 EV 富含细胞外相关和信号蛋白，网络分析表明代谢、免疫和基底膜相关蛋白富集。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、肌肉和排泄组织。EV 蛋白与秀丽隐杆线虫全基因组微阵列数据库的一个大型数据库进行的无偏比较显示，与衰老和免疫相关的基因集有显著重叠。总之，我们的数据表明，秀丽隐杆线虫可能是一个很有前途的体内模型，可用于研究 EV 在各种环境（包括衰老、代谢和免疫反应）中的遗传学和生理学。
