The cerebral cortex contains billions of neurons, and their disorganization or misspecification leads to neurodevelopmental disorders. Understanding how the plethora of projection neuron subtypes are generated by cortical neural stem cells (NSCs) is a major challenge. Here, we focused on elucidating the transcriptional landscape of murine embryonic NSCs, basal progenitors (BPs), and newborn neurons (NBNs) throughout cortical development. We uncover dynamic shifts in transcriptional space over time and heterogeneity within each progenitor population. We identified signature hallmarks of NSC, BP, and NBN clusters and predict active transcriptional nodes and networks that contribute to neural fate specification. We find that the expression of receptors, ligands, and downstream pathway components is highly dynamic over time and throughout the lineage implying differential responsiveness to signals. Thus, we provide an expansive compendium of gene expression during cortical development that will be an invaluable resource for studying neural developmental processes and neurodevelopmental disorders.

中文翻译：

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时间和顺序转录动力学定义了皮质发生中的谱系转变

大脑皮层含有数十亿个神经元，它们的紊乱或错误指定会导致神经发育障碍。了解皮质神经干细胞（NSC）如何产生大量的投射神经元亚型是一个重大挑战。在这里，我们重点阐明小鼠胚胎 NSC、基底祖细胞 (BP) 和新生神经元 (NBN) 在整个皮质发育过程中的转录景观。我们发现转录空间随时间的动态变化以及每个祖群体内的异质性。我们识别了 NSC、BP 和 NBN 簇的特征标志，并预测有助于神经命运规范的活跃转录节点和网络。我们发现受体、配体和下游通路成分的表达随着时间的推移和整个谱系是高度动态的，这意味着对信号的不同反应。因此，我们提供了皮质发育过程中基因表达的广泛概要，这将是研究神经发育过程和神经发育障碍的宝贵资源。