RNA FISH probe sequence.

In early postnatal brain, the prefrontal cortex (PFC) remains immature and highly plastic, particularly for the intratelencephalic (IT) neurons. However, the spatiotemporal molecular and cellular dynamics of PFC during this period remain poorly characterized. Here, we performed spatiotemporal single-cell RNA analysis on mouse PFC during different postnatal time points and systematically delineated the molecular and cellular dynamics of mouse PFC during early postnatal development, among which IT neurons exhibit most dramatic alterations. Based on these comprehensive spatiotemporal atlases of PFC, we deciphered the time-specific molecular and cellular characteristics during the maturation process of IT neurons in PFC, particularly the dynamic expression programs of genes regulating axon development and synaptic formation, and the risk genes of neurological developmental diseases. Furthermore, we revealed the dynamic neuron-glia interaction patterns and the underlying signaling pathways during early postnatal period. Our study provided a comprehensive resource and important insights for PFC development and PFC-associated neurological diseases.

在出生后早期的大脑中，前额叶皮层（prefrontal cortex, PFC）尚未成熟且具有高度可塑性，这一特征在端脑内投射神经元（intratelencephalic, IT）中尤为显著。然而，目前对于该时期前额叶皮层的时空分子与细胞动态变化特征仍缺乏充分解析。本研究针对不同出生后时间节点的小鼠前额叶皮层开展了时空单细胞RNA分析，系统刻画了小鼠前额叶皮层在出生后早期发育过程中的分子与细胞动态变化，其中端脑内投射神经元的改变最为显著。基于上述完整的前额叶皮层时空图谱，本研究解析了前额叶皮层中端脑内投射神经元成熟过程中的时空特异性分子与细胞特征，特别是调控轴突发育与突触形成的基因、神经发育疾病风险基因的动态表达程序。此外，本研究还揭示了出生后早期阶段动态的神经元-胶质细胞互作模式及其潜在的信号通路。本研究为前额叶皮层发育及前额叶皮层相关神经疾病的研究提供了全面的资源与重要的理论参考。