Danilchik Michael, Tumarkin Tess
Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon, 97239.
Genesis. 2017 Jan;55(1-2). doi: 10.1002/dvg.23011.
Exosomes are small extracellular vesicles (EVs) secreted by many cell types in both normal and pathogenic circumstances. Because EVs, particularly exosomes, are known to transfer biologically active proteins, RNAs and lipids between cells, they have recently become the focus of intense interest as potential mediators of cell-cell communication, particularly in long-range and juxtacrine signaling events associated with adaptive immune function and progression of cancer. Among the EVs, exosomes appear particularly adapted for long-range delivery of cargoes between cells. Because of their association with disease states, the exciting potential for exosomes to serve as diagnostic biomarkers and as target-specific biomolecule delivery vehicles has stimulated a broad range of biomedical investigations to learn how exosomes are generated, what their cargoes are, and how they might be tailored for uptake by remote targets. Addressing these questions requires experimental models in which biochemically useful amounts of material can be harvested, gene expression easily manipulated, and interpretable biological assays developed. The early Xenopus embryo fulfills these model-system ideals in an in vivo context: during morphogenesis the embryo develops several large, fluid-filled extracellular compartments across which numerous tissue-specifying signals must cross, and which are abundantly endowed with exosomes and other EVs. Importantly, certain surface-facing tissues avidly ingest EVs during gastrulation. Recent work has demonstrated that EVs can be isolated from these interstitial spaces in amounts suitable for proteomic and transcriptomic analysis. With its large numbers, great cell size, well-understood fate map, and tolerance of a variety of experimental approaches, the Xenopus embryo provides a unique opportunity to both understand and manipulate the basic cell biology of exosomal trafficking in the context of an intact organism.
外泌体是在正常和致病情况下由多种细胞类型分泌的小细胞外囊泡（EVs）。由于已知EVs，特别是外泌体，能在细胞间传递生物活性蛋白质、RNA和脂质，它们最近作为细胞间通讯的潜在介质，尤其在与适应性免疫功能和癌症进展相关的远程和旁分泌信号事件中，成为了人们强烈关注的焦点。在EVs中，外泌体似乎特别适合在细胞间进行远程货物递送。由于它们与疾病状态相关，外泌体作为诊断生物标志物和靶向特异性生物分子递送载体的令人兴奋的潜力激发了广泛的生物医学研究，以了解外泌体是如何产生的、它们的货物是什么，以及如何对其进行改造以便被远程靶标摄取。解决这些问题需要实验模型，在该模型中可以收获生化上有用量的材料、容易操纵基因表达并开发可解释的生物学检测方法。早期非洲爪蟾胚胎在体内环境中满足了这些模型系统的理想条件：在形态发生过程中，胚胎发育出几个充满液体的大细胞外隔室，许多组织特异性信号必须穿过这些隔室，并且这些隔室富含外泌体和其他EVs。重要的是，某些面向表面的组织在原肠胚形成期间会 avidly摄取EVs。最近的研究表明，可以从这些间隙空间中分离出数量适合蛋白质组学和转录组学分析的EVs。由于其数量众多、细胞体积大、命运图谱清晰且能耐受多种实验方法，非洲爪蟾胚胎为在完整生物体的背景下理解和操纵外泌体运输的基本细胞生物学提供了独特的机会。
