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

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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.