Understanding biological heterogeneity at the single cell level is required for advancing insights into the complexity of human physiology and diseases. While advances in technological and analytical methods have afforded unprecedented glimpses of this heterogeneity, the information captured to date largely represents one-time “snap” shots of single cell physiology. To address the limits of existing methods and to accelerate discoveries from single cell studies, we developed a single-cell translocation and secretion assay (TransSeA) that supports time lapse analysis, enables molecular cargo analysis of secretions such as extracellular vesicles (EVs) from single cells, allows massively parallel single cell transfer according to user-defined cell selection criteria, and supports tracking of phenotypes between parental and progeny cells derived from single cells. To demonstrate the unique capabilities and efficiencies of the assay, we present unprecedented single cell studies related to cell secretions, EV cargos and cell intrinsic properties. Although used as examples to demonstrate the feasibility and versatility of the technology, the studies already provided insights into key unanswered questions such as the microRNAs carried by EVs, the relationships between EV secretion rates and gene expressions, and the spontaneous, trans-generational phenotypic changes in EV secretion between parental and progeny cells.

中文翻译：

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单细胞易位和分泌试验 (TransSeA)

了解单细胞水平的生物异质性需要深入了解人类生理学和疾病的复杂性。虽然技术和分析方法的进步让人们对这种异质性有了前所未有的了解，但迄今为止捕获的信息主要代表单细胞生理学的一次性“快照”。为了解决现有方法的局限性并加速单细胞研究的发现，我们开发了一种支持延时分析的单细胞易位和分泌测定 (TransSeA)，能够对来自单个细胞的细胞外囊泡 (EV) 等分泌物进行分子货物分析细胞，允许根据用户定义的细胞选择标准进行大规模并行单细胞转移，并支持跟踪来自单细胞的亲代细胞和子代细胞之间的表型。为了展示该检测的独特能力和效率，我们提出了前所未有的与细胞分泌物、EV 货物和细胞内在特性相关的单细胞研究。尽管用作示例来证明该技术的可行性和多功能性，但这些研究已经提供了对关键未解问题的见解，例如 EV 携带的 microRNA、EV 分泌率与基因表达之间的关系，以及自发的跨代表型变化在亲代细胞和子代细胞之间的 EV 分泌中。