Tietje Ashlee, Maron Kourtney N, Wei Yanzhang, Feliciano David M
Department of Biological Sciences, Clemson University, Clemson, South Carolina, United States of America.
PLoS One. 2014 Nov 24;9(11):e113116. doi: 10.1371/journal.pone.0113116. eCollection 2014.
Brain development requires precise orchestration of cellular events through the coordinate exchange of information between distally located cells. One mechanism by which intercellular communication is achieved is through the transfer of extracellular vesicles (EVs). Exosomes are EVs that carry lipids, nucleic acids, and proteins and are detectable in most biological fluids including cerebrospinal fluid (CSF). Here we report that CSF EV concentrations undergo age dependent fluctuations. We characterized EV RNA content by next generation small RNA sequencing and miRNA microarray analysis and identified a temporal shift in CSF EV content. CSF EVs encapsulated miRNAs that contain a conserved hnRNPA2/B1 recognition sequence. We found that hnRNPA2/B1-containing EVs were produced by choroid plexus epithelial cells and that hnRNPA2/B1 containing EVs decreased with age. These results provide insight into EV exchange of miRNAs within the central nervous system and a framework to understand how changes in EVs may have an important impact on brain development.
大脑发育需要通过远距离细胞间信息的协调交换来精确编排细胞事件。实现细胞间通讯的一种机制是通过细胞外囊泡(EVs)的传递。外泌体是携带脂质、核酸和蛋白质的EVs,在包括脑脊液(CSF)在内的大多数生物体液中都可检测到。在此我们报告脑脊液EV浓度会随年龄产生波动。我们通过下一代小RNA测序和miRNA微阵列分析对EV RNA含量进行了表征,并确定了脑脊液EV含量的时间变化。脑脊液EVs包裹着含有保守hnRNPA2/B1识别序列的miRNAs。我们发现含hnRNPA2/B1的EVs由脉络丛上皮细胞产生,且含hnRNPA2/B1的EVs会随着年龄增长而减少。这些结果为深入了解中枢神经系统内miRNAs的EV交换提供了思路,并为理解EVs的变化如何可能对大脑发育产生重要影响提供了一个框架。