【报告题目】The molecular basis underlying transcriptional regulation of neurogenesis and regeneration.
【地点】Med-X 108 （闵行文选楼323会议室同步视频）
【摘要】Neural stem cells (NSCs) have the ability to self-renew and differentiate into neuronal or glial cell types. In this talk I will mainly talk about the functions of one transcription factor Krüppel-like factor 4 (KLF4) in NSCs and axons regeneration. KLF4 is a zinc ?nger-containing transcription factor that regulates multiple physiological and pathological functions. It plays a critical role in maintaining self-renewal of embryonic stem cells (ESCs) and is also one of the original four factors that reprogram somatic cells into induced pluripotent stem cells. However, the function of KLF4 in lineage-committed neural stem cells (NSCs) remains unknown. In my recent study, I found KLF4 is expressed in NSCs and is down-regulated during brain development and in differentiated neurons. In contrast to its positive role in promoting self-renewal of ESCs, over-expression of KLF4 in NSCs inhibits their proliferation and differentiation. Importantly, dysregulated KLF4 in NSCs and NSCs-derived ependymal cells during development leads to hydrocephalus in transgenic mice by disrupted ependymal cilia. To have a better understanding of the role of KLF4 in NSCs and in their proliferation and differentiation in vivo, I carried out gain-of-function and loss-of-function studies by in utero electroporation in the developing mouse neocortex. I provided evidence that KLF4 regulates neurogenesis and radial migration of neurons in the developing cerebral cortex. KLF4 is also developmentally regulated in retinal ganglion cells (RGCs) and its deletion enhances axon regeneration, although the underlying mechanism is not clear. I further examined the crosstalk between KLF4 and JAK-STAT signaling and found that KLF4 associates with and blocks the activity of phosphorylated STAT3 (pSTAT3). Notably, the inhibitory function of KLF4 on STAT3 signaling contributes to the regeneration failure of injured RGCs.
【报告人简介】Dr Qin received his Ph.D. from University of Science & Technology of China (USTC), conducted his post-doctoral research at the Institute of Neuroscience in Shanghai and was employed as a Research Scientistat UT Southwestern Medical. In 2015 he joined The 10th Hospital of Tongji University.In recent years, he has been making efforts to understand the molecular mechanisms by which the behavior of NSCs is regulated and developing novel therapeutic targets for treating neurological disorders. By focusing on Krüppel-like factor 4 (KLF4), a zinc finger-containing transcriptional factor, he has demonstrated that KLF4 is involved in both proliferation and differentiation of NSCs and that its dysregulation in transgenic mice leads to disrupted ventricular cilia and hydrocephalus (S. Qin et al. 2011 ProcNatlAcadSci; S. Qin and C.L. Zhang 2012 Mol Cell Biol). He as further discovered a crosstalk between KLF4 and activated STAT3 in the regulation of axon regeneration of adult retinal ganglion cells (S. Qin et al. 2013 Nature Commun).