The stochastic dynamics and regulatory mechanisms that govern differentiation of individual human neural precursor cells (NPC) into mature neurons are currently not fully understood. Here, we used single-cell RNA-sequencing (scRNA-seq) of developing neurons to dissect/identify NPC subtypes and critical developmental stages of alternative lineage specifications. This study comprises an unsupervised, high-resolution strategy for identifying cell developmental bifurcations, tracking the stochastic transcript kinetics of the subpopulations, elucidating regulatory networks, and finding key regulators. Our data revealed the bifurcation and developmental tracks of the two NPC subpopulations, and we captured an early (24 h) transition phase that leads to alternative neuronal specifications. The consequent up-regulation and down-regulation of stage- and subpopulation-specific gene groups during the course of maturation revealed biological insights with regard to key regulatory transcription factors and lincRNAs that control cellular programs in the identified neuronal subpopulations.

目前尚不完全了解控制个体人类神经前体细胞（NPC）分化为成熟神经元的随机动力学和调控机制。在这里，我们使用发育中的神经元的单细胞RNA测序（scRNA-seq）来解剖/识别NPC亚型和替代谱系规格的关键发育阶段。这项研究包括一种无监督的高分辨率策略，用于识别细胞发育分支，跟踪亚群的随机转录动力学，阐明调控网络并寻找关键调控因子。我们的数据揭示了两个NPC亚群的分叉和发育轨迹，并且我们捕获了一个早期（24 h）过渡阶段，该阶段导致了其他神经元特征。