在哺乳动物大脑中，Notch 信号传导维持皮质干细胞库并调节神经胶质细胞的命运选择和分化。然而，Notch在调节神经胶质细胞发育中的功能及其在肿瘤发生中的作用尚不清楚。在这里，我们发现干细胞中 Rbpj 基因缺失导致 Notch 失活减少了星形胶质细胞，但增加了内部状态改变的少突胶质细胞。抑制神经胶质祖细胞中的 Notch 不会影响细胞生成，反而会加速缺乏 Notch 的少突胶质细胞祖细胞 (OPC) 和 OPC 相关神经胶质瘤的生长。我们还发现了少突胶质细胞和星形胶质细胞之间的串扰，即髓鞘形成前少突胶质细胞分泌被Notch抑制的BMP4，从而上调邻近星形胶质细胞中的GFAP表达。此外，干细胞中的Notch失活会导致神经胶质瘤亚型从星形胶质细胞相关模式转变为OPC相关模式，反之亦然。我们的研究揭示了Notch的背景依赖性功能，促进干细胞中的星形胶质细胞和星形胶质细胞相关神经胶质瘤，并抑制神经胶质祖细胞中的OPC和相关神经胶质瘤。

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.