Transcriptional Regulation and Specification of Neural Stem Cells
Transcriptional Regulation and Specification of Neural Stem Cells
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DOI：
10.1007/978-94-007-6621-1_8
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发表时间：
2013-01-01
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影响因子：
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通讯作者：
Turnley, Ann M.
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文献类型：
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作者：
Christie, Kimberly J.;Emery, Ben;Turnley, Ann M.
随着二十年前发现成人大脑含有能够产生新神经元的神经干细胞（NSC），已经进行了大量的研究来操纵这些细胞来修复受损的神经系统。在了解是什么调控成体神经干细胞的特化、增殖和分化方面已经取得了很大进展，但仍有许多问题有待确定。我们可以从了解胚胎神经干细胞如何产生成年哺乳动物神经系统这一极其复杂的器官中吸取教训。本文综述了哺乳动物神经干细胞在胚胎发育过程中的转录调控作用，并将其与成年神经干细胞/神经前体细胞（NPC）的侧脑室脑室下区（SVZ）和海马齿状回颗粒下区（SGZ）的壁龛进行了比较。正常的生理NSC/NPC调节将被探索，以及它们在神经损伤和疾病后的调节和反应。最后，将内源性NSC/NPC的转录调控与胚胎干/诱导多能干（ES/iPS）细胞衍生的NSC/NPC进行比较和对比。在神经干细胞发育成特定神经元或神经胶质谱系中转录事件的胚胎序列的重演改善了ES/iPS细胞的定向分化，并且可用于治疗目的的内源性成体神经干细胞的活化和特化。
With the discovery two decades ago that the adult brain contains neural stem cells (NSCs) capable of producing new neurons, a great deal of research has been undertaken to manipulate these cells to repair the damaged nervous system. Much progress has been made in understanding what regulates adult neural stem cell specification, proliferation and differentiation but much remains to be determined. Lessons can be learned from understanding how embryonic neural stem cells produce the exquisitely complicated organ that is the adult mammalian nervous system. This review will highlight the role of transcriptional regulation of mammalian neural stem cells during embryonic development and compare these to the adult neural stem cell/neural precursor cell (NPC) niches of the subventricular zone (SVZ) of the lateral ventricle and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Normal physiological NSC/NPC regulation will be explored, as well as their regulation and responses following neural injury and disease. Finally, transcriptional regulation of the endogenous NSC/NPCs will be compared and contrasted with embryonic stem/induced pluripotent stem (ES/iPS) cell-derived NSC/NPCs. Recapitulation of the embryonic sequence of transcriptional events in neural stem cell development into specific neuronal or glial lineages improves directed differentiation of ES/iPS cells and may be useful for activation and specification of endogenous adult neural stem cells for therapeutic purposes.