Department of Nuclear Medicine, Seoul National University College of Medicine, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Republic of Korea; School of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
School of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
Biomaterials. 2017 Jan;112:82-94. doi: 10.1016/j.biomaterials.2016.10.006. Epub 2016 Oct 5.
The effective role of exosome delivering neurogenic microRNA (miRNA) enables to induce efficient differentiation process during neurogenesis. The microfludic system capable of visualizing the exosomal behavior such as secretion, migration, and uptake of individual exosomes can be used as a robust technique to understand the exosome-mediated change of cellular behavior. Here, we developed the exosome-tracing microfluidic system to visualize exosomal transport carrying the neurogenic miRNA from leading to neighboring cells, and found a new mode of exosome-mediated cell-non-autonomous neurogenesis. The miR-193a facilitated neurogenesis in F11 cells by blocking proliferation-related target genes. In addition to time-lapse live-cell imaging using microfluidics visualized the convective transport of exosomes from differentiated to undifferentiated cells. Individual exosomes containing miR-193a from differentiated donor cells were taken up by undifferentiated cells to lead them to neurogenesis. Induction of anti-miR-193a was sufficient to block neurogenesis in F11 cells. Inhibition of the exosomal production by manumycin-A and treatment of anti-miR-193a in the differentiated donor cells failed to induce neurogenesis in undifferentiated recipient cells. These findings indicate that exosomes of neural progenitors and neurogenic miRNA within these exosomes propagate cell-non-autonomous differentiation to neighboring progenitors, to delineate the roles of exosome mediating neurogenesis of population of homologous neural progenitor cells.
外泌体传递神经营养 microRNA（miRNA）的有效作用能够在神经发生过程中诱导有效的分化过程。能够可视化外泌体行为（如分泌、迁移和摄取单个外泌体）的微流控系统可用作一种强大的技术，以了解外泌体介导的细胞行为变化。在这里，我们开发了外泌体追踪微流控系统，以可视化携带神经营养 miRNA 的外泌体从主导细胞到邻近细胞的运输，并发现了一种新的外泌体介导的非自主神经发生模式。miR-193a 通过阻断增殖相关靶基因促进 F11 细胞的神经发生。除了使用微流控进行的延时活细胞成像外，还可视化了外泌体从分化细胞到未分化细胞的对流运输。来自分化供体细胞的含有 miR-193a 的单个外泌体被未分化细胞摄取，导致它们向神经发生。诱导抗 miR-193a 足以阻断 F11 细胞的神经发生。用马麦霉素 A 抑制外泌体的产生和在分化供体细胞中处理抗 miR-193a 未能诱导未分化受体细胞的神经发生。这些发现表明，神经祖细胞的外泌体和这些外泌体中的神经营养 miRNA 传播非自主分化到邻近的祖细胞，以描绘外泌体介导的同源神经祖细胞群体的神经发生作用。
