Feliciano David M, Zhang Shiliang, Nasrallah Carole M, Lisgo Steven N, Bordey Angélique
Departments of Neurosurgery, and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Institute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle upon Tyne, United Kingdom.
PLoS One. 2014 Feb 12;9(2):e88810. doi: 10.1371/journal.pone.0088810. eCollection 2014.
During brain development, neural stem cells (NSCs) receive on-or-off signals important for regulating their amplification and reaching adequate neuron density. However, how a coordinated regulation of intracellular pathways and genetic programs is achieved has remained elusive. Here, we found that the embryonic (e) CSF contains 10¹² nanoparticles/ml (77 nm diameter), some of which were identified as exosome nanovesicles that contain evolutionarily conserved molecules important for coordinating intracellular pathways. eCSF nanovesicles collected from rodent and human embryos encapsulate protein and microRNA components of the insulin-like growth factor (IGF) signaling pathway. Supplementation of eCSF nanovesicles to a mixed culture containing eNSCs activated the IGF-mammalian target of rapamycin complex 1 (mTORC1) pathway in eNSCs and expanded the pool of proliferative eNSCs. These data show that the eCSF serves as a medium for the distribution of nanovesicles, including exosomes, and the coordinated transfer of evolutionary conserved molecules that regulate eNSC amplification during corticogenesis.
在大脑发育过程中，神经干细胞（NSCs）接收对调节其增殖及达到足够神经元密度至关重要的开或关信号。然而，细胞内信号通路和基因程序如何实现协同调节仍不清楚。在此，我们发现胚胎（e）脑脊液含有10¹²个纳米颗粒/毫升（直径77纳米），其中一些被鉴定为外泌体纳米囊泡，其包含对协调细胞内信号通路很重要的进化保守分子。从啮齿动物和人类胚胎收集的eCSF纳米囊泡包裹胰岛素样生长因子（IGF）信号通路的蛋白质和微小RNA成分。将eCSF纳米囊泡添加到含有eNSCs的混合培养物中，可激活eNSCs中的IGF-雷帕霉素复合物1（mTORC1）信号通路，并扩大增殖性eNSCs库。这些数据表明，eCSF作为纳米囊泡（包括外泌体）分布的介质，以及在皮质发生过程中调节eNSC增殖的进化保守分子的协同传递介质。
