Exosomes as Novel Regulators of Adult Neurogenic Niches.
Exosomes as Novel Regulators of Adult Neurogenic Niches.
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DOI：
10.3389/fncel.2015.00501
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发表时间：
2015
影响因子：
5.3
通讯作者：
Wyneken U
中科院分区：
文献类型：
--
作者：
Bátiz LF;Castro MA;Burgos PV;Velásquez ZD;Muñoz RI;Lafourcade CA;Troncoso-Escudero P;Wyneken U
成年期的神经发生在哺乳动物大脑的两个区域得到了令人信服的证实：海马齿状回（DG）的颗粒下区（SGZ）和侧脑室（LV）的脑室下区（SVZ）。SGZ新生神经元的目的是颗粒细胞层（GCL）的DG，而新的神经元从SVZ神经元迁移到嗅球（OB）。成体神经发生的过程持续整个生命，并由神经干细胞（NSC）池支持，这些神经干细胞驻留在一个独特的和专门的微环境中，称为“神经原性生态位”。神经原性小生境由不同细胞类型的复杂组织构成，包括神经干细胞谱系、神经胶质细胞和血管细胞。因此，细胞间通讯在动态调节成人神经原性过程的稳态和可塑性中起着关键作用。特定的细胞间接触和细胞外信号提供了必要的支持，并调节神经干细胞自我更新和分化之间的平衡。此外，起源于远处位置（包括其他脑区域或全身器官）的细胞外信号可以通过脑脊液（CSF）或脉管系统到达龛并影响其性质。一些分泌的分子，如细胞因子，生长因子，神经递质和激素，在成人神经干细胞的生物学中的作用，已被系统地解决。有趣的是，除了这些公认的信号外，最近还发现了一种新型的细胞间信使：细胞外囊泡（EV）。EV，特别是外泌体，涉及mRNA、微小RNA（miRNA）、蛋白质和脂质在细胞之间的转移，因此能够改变受体细胞的功能。外泌体似乎在不同的干细胞生态位中发挥重要作用，例如间充质干细胞生态位、癌症干细胞生态位和转移前生态位;然而，它们在成人神经源性生态位中的作用几乎仍未探索。本文综述了目前关于成人SVZ和SGZ神经源性龛的细胞和细胞外成分之间的功能关系的知识，以及越来越多的证据支持外泌体在成人神经发生的生理和病理学中的潜在作用。
Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as “neurogenic niche”. Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles in adult neurogenic niches remain virtually unexplored. This review focuses on the current knowledge regarding the functional relationship between cellular and extracellular components of the adult SVZ and SGZ neurogenic niches, and the growing evidence that supports the potential role of exosomes in the physiology and pathology of adult neurogenesis.