胞外囊泡中蛋白质的共富集
Co-Enrichment of Proteins in Extracellular Vesicles
AI总结：
该研究提出并定义了蛋白质共富集（CoEn）方法，用于量化蛋白质在胞外囊泡中的共富集或共耗尽情况，并通过实验验证了其在生物发生途径调节中的应用及在EV生物制造中的潜在价值。
摘要：
胞外囊泡（EVs）是细胞分泌的物质，通过其多样的货物如蛋白质来介导组织稳态和细胞间通讯。不同的EV生物发生途径表明，共享生物发生途径的蛋白质具有特定的关联和共富集，而不同途径的蛋白质则呈现非关联和共耗尽。然而，这些关联却无法通过传统的蛋白质表达或共表达测量来检测。在这里，我们提出并定义了成对蛋白质共富集（CoEn）以量化给定蛋白质相对于其整体表达是否与另一个蛋白质共富集或共耗尽。我们使用抗体微阵列测量了EVs中多达240对蛋白质的CoEn和差异CoEn（dCoEn）。我们通过调节已知的EV生物发生途径验证了CoEn，并发现dCoEn在扰动和参考条件之间量化了预期的变化并揭示了新的变化；在三种模型细胞系以及母体和器官趋向性乳腺癌后代细胞系中，CoEn和dCoEn揭示了既保持又变化的CoEn，这可能值得进一步研究。总体而言，我们的结果表明，CoEn反映了并揭示了细胞生理和EV生物发生，易于测量，并且可以进一步作为EV生物制造中的质量控制以及新的EV生物标志物的基础。
英文摘要：
Extracellular vesicles (EVs) are cell-derived secretions that mediate tissue homeostasis and intercellular communication through their diverse cargos, such as proteins. Distinct EV biogenesis pathways suggest specific association and co-enrichment of proteins sharing a biogenesis pathway, and non-association and co-depletion of proteins segregated into distinct pathways. Yet these associations elude conventional protein expression or co-expression measurements. Here, we propose and define pairwise protein co-enrichment (CoEn) to quantify whether a given protein is co-enriched or co-depleted with another protein relative to its overall expression. We measure CoEn, and differential CoEn (dCoEn) between a stimulus and a reference condition, of up to 240 protein pairs in EVs using antibody microarrays. We validate CoEn by modulating well-known EV biogenesis pathways, and find that dCoEn quantifies expected changes between perturbed and reference conditions while uncovering new ones; CoEn and dCoEn in three model cell lines and parental and organotropic breast cancer progeny cell lines reveals both preserved and variable CoEn that may warrant further studies. Collectively, our result suggest that CoEn reflects and illuminates cell physiology and EV biogenies, is readily measurable, and could further serve as quality control in EV biomanufacturing as well as underpin new EV biomarkers.
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