Development of an Adult CNS Stem Cell Marking System

神经发生在成人大脑中的离散区域继续，包括海马区和脑室下区。成人海马区神经发生的确切功能意义仍在争论中。然而，海马神经发生的改变可能在许多神经精神障碍中起到病理生理学作用。目前，成人脑中的祖细胞最常见的鉴定方法是溴脱氧尿嘧啶核苷(BrdU)标记，并结合特异性分化标记物鉴定其命运。然而，这一方法受到若干限制，包括敏感性和持久性问题。在这里，我们建议使用基于绿色荧光蛋白(GFP)的转基因系统，该系统利用Cre重组酶位点特异的DNA重组系统和lac阻遏物可诱导/调节系统来开发一种有效的方法来永久标记成人脑内Nestin系中枢神经系统干细胞。这一系统将允许巢蛋白谱系干细胞在成人大脑中无限期地跟随其命运，无论它们沿着神经元还是非神经元分化。

Neurogenesis continues in adult brain in discrete regions including the hippocampus and the subventricular zone. The exact functional significance of neurogenesis in adult hippocampus is still being debated. However altered hippocampal neurogenesis may play a pathophysiological role in a number of neuropsychiatric disorders. Presently progenitor cells in adult brain are most commonly identified by bromodeoxyuridine (BrdU) labeling and their fate followed with specific differentiation markers. However this methodology suffers several limitations including issues of sensitivity and permanence. Here we propose to use a green fluorescent protein (GFP) based transgenic system that utilizes the Cre recombinase site specific DNA recombination system and the lac repressor inducible/regulatable system to develop an efficient method for permanently marking nestin lineage CNS stem cells in adult brain. This system will allow the fate of nestin lineage stem cells to be followed indefinitely in adult brain irrespective of their differentiation along neuronal or non-neuronal lines.