Department of Biological Sciences, Clemson University, Clemson, SC 29634-0314, USA.
Department of Biological Sciences, Clemson University, Clemson, SC 29634-0314, USA.
Cell Rep. 2018 Apr 3;23(1):78-89. doi: 10.1016/j.celrep.2018.03.037.
Subventricular zone (SVZ) neural stem cells (NSCs) are the cornerstone of the perinatal neurogenic niche. Microglia are immune cells of the nervous system that are enriched in the neonatal SVZ. Although microglia regulate NSCs, the extent to which this interaction is bi-directional is unclear. Extracellular vesicles (EVs) are cell-derived particles that encase miRNA and proteins. Here, we demonstrate that SVZ NSCs generate and release EVs. Neonatal electroporated fluorescent EV fusion proteins were released by NSCs and subsequently cleared from the SVZ. EVs were preferentially targeted to microglia. Small RNA sequencing identified miRNAs within the EVs that regulate microglia physiology and morphology. EVs induced a transition to a CD11b/Iba1 non-stellate microglial morphology. The transition accompanied a microglial transcriptional state characterized by Let-7-regulated cytokine release and a negative feedback loop that controlled NSC proliferation. These findings implicate an NSC-EV-microglia axis and provide insight to normal and pathophysiological brain development.
室下区 (SVZ) 神经干细胞 (NSCs) 是围产期神经发生龛的基石。小胶质细胞是富含于新生 SVZ 的神经系统免疫细胞。尽管小胶质细胞调节 NSCs，但这种相互作用的程度尚不清楚。细胞外囊泡 (EVs) 是包裹 miRNA 和蛋白质的细胞衍生颗粒。在这里，我们证明了 SVZ NSCs 能够产生和释放 EVs。新生电穿孔荧光 EV 融合蛋白由 NSCs 释放，并随后从 SVZ 中清除。EVs 优先靶向小胶质细胞。小 RNA 测序确定了 EV 内调节小胶质细胞生理学和形态的 miRNA。EVs 诱导 CD11b/Iba1 非星状小胶质细胞形态的转变。这种转变伴随着小胶质细胞转录状态的特征，表现为 Let-7 调节的细胞因子释放和负反馈环，控制 NSC 增殖。这些发现表明存在一个 NSC-EV-小胶质细胞轴，并为正常和病理生理脑发育提供了深入了解。
