Development of an Adult CNS Stem Cell Marking System

在成年人的大脑中，神经发生在包括海马和脑室下区在内的离散区域中继续。成年海马神经发生的确切功能意义仍有争议。然而，海马神经发生的改变可能在许多神经精神疾病中发挥病理生理作用。 目前，成人脑中的祖细胞最常通过溴脱氧尿苷（BrdU）标记来鉴定，并且其命运随后是特异性分化标记物。然而，这种方法有一些局限性，包括敏感性和持久性问题。在这里，我们建议使用一个绿色荧光蛋白（GFP）为基础的转基因系统，利用Cre重组酶位点特异性DNA重组系统和乳糖阻遏物诱导/调节系统开发一种有效的方法永久标记巢蛋白谱系CNS干细胞在成年人的大脑。该系统将允许巢蛋白谱系干细胞的命运在成人脑中无限期地跟随，而不管它们沿着神经元或非神经元系的分化。

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.