To unravel the epigenetic regulation pathway of hippocampal neurogenesis in the adult mammalian brain, provide molecular insights of relevant human disease

揭示成年哺乳动物大脑海马神经发生的表观遗传调控途径，为相关人类疾病提供分子见解

• 批准号: 203348008
• 负责人: Dr. Hai-Kun Liu, Ph.D.
• 金额: --
• 依托单位: Abteilung Molekulare Neurogenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/203348008?language=en
• 关键词: unravel; epigenetic; regulation; pathway; hippocampal

Epigenetic mechanisms are crucial for the regulation of the most important characteristics of stem cells that are self-renewal and multipotency. The aim of this project is to investigate the role of the chromatin-remodeling factor CHD7 in hippocampal neural stem cells (NSCs) and neurogenesis. CHD7 mutation in human causes severe developmental disease, CHARGE syndrome. Thus CHD7 may serve as a master epigenetic regulator of multiple tissue specific stem cells. We will first analyze the function of CHD7 in fetal and adult NSCs both in animal models and in cultured NSCs, in particular the role of CHD7 in maintenance of adult NSCs and adult neurogenesis in the hippocampus. The co-factors of CHD7 in regulation of chromatin structure will be further identified using mass spectrometry. In addition, we will perform chromatin immunoprecipitation sequencing (ChIP-Seq) experiment in order to identify the molecular network directly controlled by CHD7 in NSCs. This will greatly improve our understanding of the role of epigenetic mechanism in regulation of adult hippocampal neurognesis, and possibly provide clinical implication for the human CHARGE syndrome.

表观遗传机制对于调节干细胞最重要的特征是自我更新和多能性是至关重要的。本研究旨在探讨染色质重塑因子CHD 7在海马神经干细胞（NSCs）和神经发生中的作用。人类CHD 7突变导致严重的发育性疾病，CHARGE综合征。因此，CHD 7可以作为多种组织特异性干细胞的主要表观遗传调节因子。我们将首先在动物模型和培养的NSC中分析CHD 7在胎儿和成人NSC中的功能，特别是CHD 7在维持成人NSC和海马中的成人神经发生中的作用。将使用质谱法进一步鉴定CHD 7在调节染色质结构中的辅因子。此外，我们将进行染色质免疫沉淀测序（ChIP-Seq）实验，以确定神经干细胞中CHD 7直接控制的分子网络。这将极大地提高我们对成年海马神经生长调控的表观遗传机制的理解，并可能为人类CHARGE综合征提供临床意义。