Orphan nuclear receptor TLX signaling in neural stem cells

神经干细胞中的孤儿核受体 TLX 信号传导

• 批准号: 7296706
• 负责人: YANHONG SHI
• 金额: $ 36.97万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7296706
• 关键词: 3' Untranslated Regions; Adult; Alzheimer' s Disease; Base Pairing; Brain; Brain Injuries; CDKN1A gene; Cell Maintenance; Cell Proliferation; Cell physiology; Cells; Clinic; Co-Immunoprecipitations; Disease; Dominant-Negative Mutation; Drosophila genus; Ectopic Expression; Elements; Fibrinogen; Functional RNA; Gene Expression; Gene Targeting; Genes; Genetic Transcription; Growth; HDAC5 gene; Histone Deacetylase; Histones; Homologous Gene; In Vitro; Knockout Mice; Laboratories; Mass Spectrum Analysis; Messenger RNA; MicroRNAs; Molecular Target; Neurodegenerative Disorders; Neurons; Nuclear Orphan Receptor; Nuclear Receptors; Null Lymphocytes; Parkinson Disease; Peptides; Play; Process; Proliferating; Prosencephalon; Protein Overexpression; Proteins; Proteomics; Recruitment Activity; Regulation; Replacement Therapy; Repression; Research Personnel; Role; Signal Pathway; Signal Transduction; Small Interfering RNA; Stem cells; Testing; Time; Transcription Repressor/Corepressor; Transgenic Organisms; Translational Repression; Undifferentiated; base; bench to bedside; cell type; chromatin immunoprecipitation; gain of function; human disease; insight; interdisciplinary approach; loss of function; mouse model; mutant; nerve stem cell; novel; oncoprotein p21; programs; promoter; self-renewal; stem cell technology

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.

描述（由申请人提供）：干细胞技术对治疗目前缺乏有效治疗的各种人类疾病具有很大的希望。确定控制干细胞自我更新的因素是将干细胞技术从实验室推向临床的重要一步。孤儿核受体TLX在调节这一过程中起重要作用。TLX在哺乳动物大脑中特异性表达，对维持成体神经干细胞处于未分化和自我再生状态至关重要。本研究的目的是通过鉴定其下游靶基因和上游调控因子来揭示TLX的调控级联。这项研究将对实施基于神经干细胞的细胞替代疗法治疗神经退行性疾病（如阿尔茨海默病和帕金森病）和脑损伤至关重要。本研究结果将为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控因子，都将成为干预神经退行性疾病的新分子靶点。