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Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination / 神经科学通报·英文版
Neuroscience Bulletin ; (6): 247-260, 2018.
Artigo em Inglês | WPRIM | ID: wpr-777042
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.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Fisiologia / Fatores de Transcrição / Lisofosfatidilcolinas / Diferenciação Celular / Oligodendroglia / Doenças Desmielinizantes / Biologia Celular / Toxicidade / Células Precursoras de Oligodendrócitos / Remielinização Limite: Animais Idioma: Inglês Revista: Neuroscience Bulletin Ano de publicação: 2018 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Fisiologia / Fatores de Transcrição / Lisofosfatidilcolinas / Diferenciação Celular / Oligodendroglia / Doenças Desmielinizantes / Biologia Celular / Toxicidade / Células Precursoras de Oligodendrócitos / Remielinização Limite: Animais Idioma: Inglês Revista: Neuroscience Bulletin Ano de publicação: 2018 Tipo de documento: Artigo