Single-cell spatiotemporal transcriptome dynamics of mouse prefrontal cortex intratelencephalic neurons during postnatal development

The prefrontal cortex (PFC) is a core regulatory center for higher cognitive functions in the mammalian brain. In early postnatal mice, the PFC remains incompletely mature, particularly the intratelencephalic (IT) neurons located in superficial layers. However, the molecular developmental trajectories and regulatory mechanisms of IT neurons during the critical postnatal period (1-2 weeks) for circuit establishment, remain poorly characterized at single-cell resolution. Here, we performed single-cell RNA sequencing analysis on mouse PFC isolated at different developmental time points, and integrated with spatial transcriptomic data. Our study systematically deciphered the spatiotemporal transcriptome dynamics of mouse PFC during postnatal development, with particular emphasis on the heterogeneity of IT neurons. We identified dynamically expressed genes during postnatal development, including cadherin and axon guidance molecule genes, as well as specific transcriptional regulators that control the maturation of IT neurons in different layers. Furthermore, we also revealed that glial cells play crucial regulatory roles in IT neuron development through specific signaling pathways. Our study provides a comprehensive single-cell atlas of postnatal mouse PFC development, offering important insights into the mechanisms of neural development and circuit assembly in PFC. To delineate the molecular trajectories underlying postnatal development of prefrontal cortex (PFC) neurons and investigate the mechanisms governing early neural circuit assembly, we performed high-throughput single-cell RNA sequencing (scRNA-seq) on PFC tissues from mice across key developmental timepoints (postnatal day: P1, P4, P10 and adulthood: P84). Our comprehensive transcriptomic atlas captured dynamic gene expression patterns during critical stages of neuronal maturation.