The dorsal and ventral human telencephalons contain different neuronal subtypes, including glutamatergic, GABAergic, and cholinergic neurons, and how these neurons are generated during early development is not well understood. Using scRNA-seq and stringent validations, we reveal here a developmental roadmap for human telencephalic neurons. Both dorsal and ventral telencephalic radial glial cells (RGs) differentiate into neurons via dividing intermediate progenitor cells (IPCs_div) and early postmitotic neuroblasts (eNBs). The transcription factor ASCL1 plays a key role in promoting fate transition from RGs to IPCs_div in both regions. RGs from the regionalized neuroectoderm show heterogeneity, with restricted glutamatergic, GABAergic, and cholinergic differentiation potencies. During neurogenesis, IPCs_div gradually exit the cell cycle and branch into sister eNBs to generate distinct neuronal subtypes. Our findings highlight a general RGs-IPCs_div-eNBs developmental scheme for human telencephalic progenitors and support that the major neuronal fates of human telencephalon are predetermined during dorsoventral regionalization with neuronal diversity being further shaped during neurogenesis and neural circuit integration.

中文翻译：

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早期人类端脑的发育编程和谱系分支

背侧和腹侧人类端脑包含不同的神经元亚型，包括谷氨酸能、GABA 能和胆碱能神经元，而这些神经元在早期发育过程中是如何产生的尚不清楚。使用 scRNA-seq 和严格的验证，我们在这里揭示了人类端脑神经元的发展路线图。背侧和腹侧端脑放射状胶质细胞 (RGs) 通过分裂中间祖细胞 (IPCs_div) 和早期有丝分裂后成神经细胞 (eNBs) 分化成神经元。转录因子 ASCL1 在促进两个区域从 RGs 到 IPCs_div 的命运转变中起关键作用。来自区域化神经外胚层的 RG 表现出异质性，具有受限的谷氨酸能、GABA 能和胆碱能分化能力。在神经发生过程中，IPCs_div 逐渐退出细胞周期并分支到姐妹 eNB 以生成不同的神经元亚型。我们的研究结果强调了人类端脑祖细胞的一般 RGs-IPCs_div-eNBs 发育方案，并支持人类端脑的主要神经元命运在背腹区域化过程中预先确定，神经元多样性在神经发生和神经回路整合过程中进一步形成。