Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination

作     者：Yanqing Shi Qi Shao Zhenghao Li Ginez A. Gonzalez Fengfeng Lu Dan Wang Yingyan Pu Aijun Huang Chao Zhao Cheng He Li Cao 

作者机构：Institute of Neuroscience Key Laboratory of Molecular Neurobiology of The Ministry of Education and The Collaborative Innovation Center for Brain Science Second Military Medical University Shanghai 200433 China Institute of Health Sciences Anhui University Hefei 230601China Wellcome Trust-Medical Research Council Stem Cell Insti-tute University of Cambridge Cambridge CB2 0AH UK 

出 版 物：《Neuroscience Bulletin》 (神经科学通报（英文版）)

年 卷 期：2018年第34卷第2期

页      面：247-260页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the International Cooperation and Exchange Program of the National Natural Science Foundation of China(81461138035) the National Natural Science Foundation of China(81371326,31571066,and 31371068) the National Basic Research Development Program of China(2016YFA0100802) the UK Medical Research Council(MR/M010503/1) the UK Multiple Sclerosis Society(33) 

主　　题：Myt1L Oligodendrocyte precursor cells Remyelination Demyelination Olig1 

摘      要：The differentiation and maturation of oligodendrocyte precursor cells(OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1 L(myelin transcription factor 1-like), mainly expressed in neurons,has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1 L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1 L in neuron/glia antigen 2-positive(NG2+)OPCs was significantly higher than that in mature CC1+oligodendrocytes. In primary cultured OPCs,overexpression of Myt1 L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1 L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. Ch IP assays showed that Myt1 L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1 L is an essential regulator of OPC differentiation, thereby supporting Myt1 L as a potential therapeutic target for demyelinating diseases.