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

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Abstract

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. Myt1L (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 Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2+) OPCs was significantly higher than that in mature CC1+ oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.

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Acknowledgements

This work was 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), and the UK Multiple Sclerosis Society (33).

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  1. Yanqing Shi, Qi Shao and Zhenghao Li have contributed equally to this work.

Authors and Affiliations

  1. 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

    Yanqing Shi, Qi Shao, Zhenghao Li, Fengfeng Lu, Dan Wang, Yingyan Pu, Aijun Huang, Cheng He & Li Cao

  2. Institute of Health Sciences, Anhui University, Hefei, 230601, China

    Fengfeng Lu

  3. Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, CB2 0AH, UK

    Ginez A. Gonzalez & Chao Zhao

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  1. Yanqing Shi
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Correspondence to Cheng He or Li Cao.

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Shi, Y., Shao, Q., Li, Z. et al. Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination. Neurosci. Bull. 34, 247–260 (2018). https://doi.org/10.1007/s12264-018-0207-9

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