Orphan nuclear receptor TLX signaling in neural stem cells

描述(申请人提供)：干细胞技术为目前缺乏有效疗法的各种人类疾病的治疗提供了巨大的希望。识别控制干细胞自我更新的因素是将干细胞技术从实验室转移到临床的重要一步。在调节这一过程中起重要作用的一个因素是孤儿核受体TLX。TLX在哺乳动物的大脑中特异表达，对维持成年神经干细胞处于未分化和自我更新状态是必不可少的。这项研究的目的是通过确定TLX的下游靶基因和上游调控因子来揭示TLX的调节级联反应。这项研究将对基于神经干细胞的替代疗法的实施至关重要，该疗法用于治疗阿尔茨海默病、帕金森病和脑损伤等神经退行性疾病。这项研究的结果将为TLX信号通路提供新的见解，并定义控制神经干细胞维持和自我更新的新元件。TLX信号网络的每个组成部分，无论是下游靶基因还是上游调节因子，都将成为干预神经退行性疾病的新的分子靶点。

DESCRIPTION (provided by applicant): Stem cell technology holds great promise for the treatment of a variety of human diseases that currently lack effective therapies. Identifying factors that control stem cell self-renewal is an important step in moving stem cell technology from the laboratory to the clinics. One factor that plays an important role in regulating this process is orphan nuclear receptor TLX. TLX is specifically expressed in mammalian brains and is essential to maintain adult neural stem cells in the undifferentiated and self-renewable state. The objective of this study is to uncover the regulatory cascade of TLX by identifying its downstream target genes and upstream regulators. This study will be critical to the implementation of neural stem cell-based cell replacement therapy for the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases and brain injuries. The results of this study will provide new insights into TLX signaling pathway and define novel elements that control neural stem cell maintenance and self-renewal. Each component of the TLX signaling network, either downstream target genes or upstream regulators, will be novel molecular targets for intervening neurodegenerative diseases.