Genetic Analysis of Neural Stem Cells

描述（由申请人提供）： 神经干细胞（Neural stem cells，NSCs）是一类具有自我更新和分化为神经元和神经胶质的多能细胞。已经提出将NSC植入作为多种人类神经系统疾病的治疗方法，然而，对该细胞群体的产生、效力和更新能力的遗传控制尚未完全理解。该提议基于PI实验室中的意外观察结果，即特定锌指蛋白的缺失损害了前脑脑室下区的NSC在体内和体外的增殖。本研究的目的是验证以下假设：（1）该转录调节因子控制神经干细胞和多能祖细胞的自我更新和潜能;（2）该因子的缺失导致以更新为代价的过早分化;以及（3）该因素通过滴定分化的可用性来起作用-在没有分化信号的情况下通过形成异聚复合物促进转录调节因子。

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.