Department of Pharmacology and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Pharmacology and Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Stem Cell Reports. 2018 Mar 13;10(3):1146-1159. doi: 10.1016/j.stemcr.2018.01.018. Epub 2018 Mar 1.
Quiescent neural stem cells (qNSCs) with radial morphology are the only proven source of new neurons in the adult mammalian brain. Our understanding of the roles of newly generated neurons depends on the ability to target and manipulate adult qNSCs. Although various strategies have been developed to target and manipulate adult hippocampal qNSCs, they often suffer from prolonged breeding, low recombination efficiency, and non-specific labeling. Therefore, developing a readily manufactured viral vector that allows flexible packaging and robust expression of various transgenes in qNSCs is a pressing need. Here, we report a recombinant adeno-associated virus serotype 4 (rAAV4)-based toolkit that preferentially targets hippocampal qNSCs and allows for lineage tracing, functional analyses, and activity manipulation of adult qNSCs. Importantly, targeting qNSCs in a non-Cre-dependent fashion opens the possibility for studying qNSCs in less genetically tractable animal species and may have translational impact in gene therapy by preferentially targeting qNSCs.
静息态神经干细胞（qNSCs）具有放射状形态，是成年哺乳动物大脑中新生神经元的唯一已知来源。我们对新生成的神经元的作用的理解取决于靶向和操纵成年 qNSCs 的能力。尽管已经开发了各种策略来靶向和操纵成年海马 qNSCs，但它们通常存在繁殖时间长、重组效率低和非特异性标记等问题。因此，开发一种易于制造的病毒载体，允许在 qNSCs 中灵活包装和稳健表达各种转基因，是一项紧迫的需求。在这里，我们报告了一个基于重组腺相关病毒血清型 4（rAAV4）的工具包，它可以优先靶向海马 qNSCs，并允许对成年 qNSCs 进行谱系追踪、功能分析和活性操纵。重要的是，以非 Cre 依赖性的方式靶向 qNSCs 为研究遗传上不易处理的动物物种中的 qNSCs 提供了可能性，并可能通过优先靶向 qNSCs 对基因治疗产生转化影响。
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