Proper neural progenitor behavior in conjunction with orderly vasculature formation is fundamental to the development of the neocortex. However, the mechanisms coordinating neural progenitor behavior and vessel growth remain largely elusive. Here we show that robust metabolic production of lactate by radial glial progenitors (RGPs) co-regulates vascular development and RGP division behavior in the developing mouse neocortex. RGPs undergo a highly organized lineage progression program to produce diverse neural progeny. Systematic single-cell metabolic state analysis revealed that RGPs and their progeny exhibit distinct metabolic features associated with specific cell types and lineage progression statuses. Symmetrically dividing, proliferative RGPs preferentially express a cohort of genes that support glucose uptake and anaerobic glycolysis. Consequently, they consume glucose in anaerobic metabolism and produce a high level of lactate, which promotes vessel growth. Moreover, lactate production enhances RGP proliferation by maintaining mitochondrial length. Together, these results suggest that specific metabolic states and metabolites coordinately regulate vasculature formation and progenitor behavior in neocortical development.

适当的神经祖细胞行为与有序的脉管系统形成相结合是新皮质发育的基础。然而，协调神经祖细胞行为和血管生长的机制在很大程度上仍然难以捉摸。在这里，我们展示了放射状胶质祖细胞 (RGP) 对乳酸的强劲代谢产生共同调节发育中的小鼠新皮质中的血管发育和 RGP 分裂行为。RGPs 经历了一个高度组织化的谱系进展程序，以产生不同的神经后代。系统的单细胞代谢状态分析表明，RGP 及其后代表现出与特定细胞类型和谱系进展状态相关的不同代谢特征。对称分裂的增殖性 RGP 优先表达支持葡萄糖摄取和无氧糖酵解的一组基因。因此，它们在无氧代谢中消耗葡萄糖并产生高水平的乳酸，从而促进血管生长。此外，乳酸的产生通过维持线粒体长度来增强 RGP 增殖。总之，这些结果表明特定的代谢状态和代谢物在新皮质发育中协同调节血管系统的形成和祖细胞的行为。