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Context-dependent regulation of Notch signaling in glial development and tumorigenesis.
Guo, Rongliang; Han, Danyu; Song, Xingrui; Gao, Yanjing; Li, Zhenmeiyu; Li, Xiaosu; Yang, Zhengang; Xu, Zhejun.
Afiliação
  • Guo R; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
  • Han D; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
  • Song X; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
  • Gao Y; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
  • Li Z; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
  • Li X; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
  • Yang Z; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
  • Xu Z; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China.
Sci Adv ; 9(45): eadi2167, 2023 11 10.
Article em En | MEDLINE | ID: mdl-37948517
ABSTRACT
In the mammalian brain, Notch signaling maintains the cortical stem cell pool and regulates the glial cell fate choice and differentiation. However, the function of Notch in regulating glial development and its involvement in tumorigenesis have not been well understood. Here, we show that Notch inactivation by genetic deletion of Rbpj in stem cells decreases astrocytes but increases oligodendrocytes with altered internal states. Inhibiting Notch in glial progenitors does not affect cell generation but instead accelerates the growth of Notch-deprived oligodendrocyte progenitor cells (OPCs) and OPC-related glioma. We also identified a cross-talk between oligodendrocytes and astrocytes, with premyelinating oligodendrocytes secreting BMP4, which is repressed by Notch, to up-regulate GFAP expression in adjacent astrocytes. Moreover, Notch inactivation in stem cells causes a glioma subtype shift from astroglia-associated to OPC-correlated patterns and vice versa. Our study reveals Notch's context-dependent function, promoting astrocytes and astroglia-associated glioma in stem cells and repressing OPCs and related glioma in glial progenitors.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neurogênese / Glioma Limite: Animals Idioma: En Revista: Sci Adv Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neurogênese / Glioma Limite: Animals Idioma: En Revista: Sci Adv Ano de publicação: 2023 Tipo de documento: Article