报告题目:Sequential activation of two feed-forward loops to efficiently convert human fibroblasts to functional neurons
报告人:付向东,加州大学圣地亚哥分校细胞与分子医学系终身教授,
武汉大学生命科学学院客座教授,中国科学院生物物理研究所中科院核酸生物学重点实验室主任
报告简介:Direct conversion of somatic cells into neurons holds great promise for regenerative medicine. However, as neuronal conversion is relatively inefficient on human cells compared to mouse cells, it has been unclear what might be key barriers to reprogramming in human cells. We recently elucidated an RNA program mediated by the polypyrimidine tract binding protein PTB to convert mouse embryonic fibroblasts (MEFs) into functional neurons. On human adult fibroblasts (HAFs), however, we unexpectedly find that invoke of the documented PTB-REST-miR-124 loop only generates immature neurons. We now report that the functionality requires sequential inactivation of PTB and the PTB paralog nPTB in HAFs. Inactivation of nPTB triggers another self-enforcing loop essential for neuronal maturation, which comprises nPTB, the transcription factor BRN2, and miR-9. These findings suggest two separate gatekeepers to control neuronal conversion and maturation and consecutively overcoming these gatekeepers enables deterministic reprogramming of HAFs into functional neurons.
讲座时间:4月18日上午10:00
讲座地点:药学院 426学术报告厅
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