Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA.
J Cell Biol. 2021 Sep 6;220(9). doi: 10.1083/jcb.202101075. Epub 2021 Jul 26.
Extracellular vesicles (EVs) are thought to mediate the transport of proteins and RNAs involved in intercellular communication. Here, we show dynamic changes in the buoyant density and abundance of EVs that are secreted by PC12 cells stimulated with nerve growth factor (NGF), N2A cells treated with retinoic acid to induce neural differentiation, and mouse embryonic stem cells (mESCs) differentiated into neuronal cells. EVs secreted from in vitro differentiated cells promote neural induction of mESCs. Cyclin D1 enriched within the EVs derived from differentiated neuronal cells contributes to this induction. EVs purified from cells overexpressing cyclin D1 are more potent in neural induction of mESC cells. Depletion of cyclin D1 from the EVs reduced the neural induction effect. Our results suggest that EVs regulate neural development through sorting of cyclin D1.
细胞外囊泡（EVs）被认为介导了参与细胞间通讯的蛋白质和 RNA 的运输。在这里，我们展示了受神经生长因子（NGF）刺激的 PC12 细胞、用维甲酸处理以诱导神经分化的 N2A 细胞和分化为神经元细胞的小鼠胚胎干细胞（mESCs）分泌的 EVs 的浮力密度和丰度的动态变化。来自体外分化细胞的 EVs 促进 mESCs 的神经诱导。在分化神经元细胞衍生的 EV 中富集的细胞周期蛋白 D1 有助于这种诱导。过表达细胞周期蛋白 D1 的细胞中纯化的 EVs 在 mESC 细胞的神经诱导中更有效。从 EVs 中耗尽细胞周期蛋白 D1 会降低神经诱导作用。我们的结果表明，EVs 通过细胞周期蛋白 D1 的分选来调节神经发育。
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