The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remain unknown. Here we developed a semi-automated live/fixed correlative imaging method to map basal radial glial cell division modes in early fetal tissue and cerebral organoids. Through the live analysis of hundreds of dividing progenitors, we show that basal radial glial cells undergo abundant symmetric amplifying divisions, and frequent self-consuming direct neurogenic divisions, bypassing intermediate progenitors. These direct neurogenic divisions are more abundant in the upper part of the subventricular zone. We furthermore demonstrate asymmetric Notch activation in the self-renewing daughter cells, independently of basal fibre inheritance. Our results reveal a remarkable conservation of fate decisions in cerebral organoids, supporting their value as models of early human neurogenesis.

人类新皮质经历了强烈的进化扩张，很大程度上是由于祖细胞群体（基底放射状胶质细胞）的增加。这些细胞负责产生多种细胞类型，但单个祖细胞所做出的连续细胞命运决定仍然未知。在这里，我们开发了一种半自动实时/固定相关成像方法来绘制早期胎儿组织和大脑类器官中的基底放射状胶质细胞分裂模式。通过对数百个分裂祖细胞的实时分析，我们发现基底放射状胶质细胞经历了丰富的对称放大分裂，以及频繁的自我消耗的直接神经源性分裂，绕过了中间祖细胞。这些直接的神经源性分裂在室下区的上部更为丰富。我们还证明了自我更新子细胞中的不对称Notch激活，与基底纤维遗传无关。我们的结果揭示了大脑类器官命运决定的显着保守性，支持了它们作为早期人类神经发生模型的价值。