Parenchymal astrocytes have emerged as a potential reservoir for new neurons in non-neurogenic brain regions. It is currently unclear how astrocyte neurogenesis is controlled molecularly. Here we show that Notch signaling-deficient astrocytes can generate new neurons after injury. Using single-cell RNA sequencing, we found that, when Notch signaling is blocked, astrocytes transition to a neural stem cell-like state. However, only after injury do a few of these primed astrocytes unfold a neurogenic program, including a self-amplifying progenitor-like state. Further, reconstruction of the trajectories of individual cells allowed us to uncouple astrocyte neurogenesis from reactive gliosis, which occur along independent branches. Finally, we show that cortical neurogenesis molecularly recapitulates canonical subventricular zone neurogenesis with remarkable fidelity. Our study supports a widespread potential of parenchymal astrocytes to function as dormant neural stem cells.

实质性星形胶质细胞已经成为非神经源性大脑区域中新神经元的潜在储存库。目前尚不清楚如何在分子上控制星形胶质细胞的神经发生。在这里，我们显示Notch信号缺陷星形胶质细胞可以在受伤后生成新的神经元。使用单细胞RNA测序，我们发现，当Notch信号被阻断时，星形胶质细胞会转变为神经干细胞样状态。然而，只有在损伤后，这些引发的星形胶质细胞中的一些才会展开神经原性程序，包括自我扩增的祖先样状态。此外，单个细胞轨迹的重建使我们能够将星形胶质细胞的神经发生与反应性胶质增生脱钩，后者沿着独立的分支发生。最后，我们表明，皮质神经发生分子以显着的保真度概括了典型的脑室下区神经发生。我们的研究支持实质性星形胶质细胞具有潜在的潜伏神经干细胞功能。