Genetic Analysis of Neural Stem Cells

描述(由申请人提供)： 神经干细胞(NSCs)是一种具有自我更新和分化为神经元和神经胶质细胞的多潜能细胞群。神经干细胞的植入已被认为是一种治疗人类多种神经系统疾病的方法，然而，对这种细胞群体的生产、潜能和更新能力的遗传控制还不完全清楚。这一建议是基于PI实验室出人意料的观察结果，即特定锌指蛋白的缺失在体内和体外都会损害前脑室下区神经干细胞的繁殖。这项提议的目的将检验以下假设：(1)该转录调控因子控制神经干细胞和多能祖细胞的自我更新和潜能；(2)缺乏该因子会导致以更新为代价的过早分化；(3)该因子通过在没有分化信号的情况下通过形成异构体复合体来滴定促进分化的转录调控因子的可用性。

DESCRIPTION (provided by applicant): Neural stem cells (NSCs) are a multipotent cell population capable of both self-renewal and differentiation into neurons and glia. Engraftment of NSCs has been proposed as a therapeutic approach for a variety of human neurological disorders, however, genetic control of the production, potency and capacity for renewal of this cell population are not fully understood. This proposal is based on unexpected observations in the PI's laboratory that deletion of a particular zinc finger protein impairs the propagation of NSCs from forebrain subventricular zone, both in vivo and in vitro. The aims of this proposal will test the hypotheses (1) that this transcriptional regulator controls self renewal and potency of NSCs and multipotent progenitors; (2) that absence of this factor results in premature differentiation at the expense of renewal; and (3) that this factor acts by titrating the availability of differentiation-promoting transcriptional regulators through the formation of heteromeric complexes in the absence of differentiation signals.