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 o...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.展开更多
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)+2 种基金the National Basic Research Development Program of China(2016YFA0100802)the UK Medical Research Council(MR/M010503/1)the UK Multiple Sclerosis Society(33)
文摘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.
