在人类大脑皮层发育过程中，多能神经前体细胞产生兴奋性神经元和胶质细胞。对转录组和表观遗传组的研究揭示了重要的基因调控网络，支持这一关键发育事件。然而，人类皮层发生过程中基因表达和蛋白质丰度的转录后控制仍然不完全清楚。我们通过使用双记者细胞系培养人类端脑组织器，分离神经前体细胞和神经元，并进行细胞类别和发育阶段特异性的转录组和蛋白质组分析，解决了这个问题。将这两个数据集整合起来，揭示了人类皮层发生过程中的基因表达模块。对其中一个模块的研究发现了mTOR介导的5'TOP元素富集的翻译机制在早期神经前体细胞中的调控。我们表明，在早期神经前体细胞中，部分抑制核糖体基因的翻译可以防止分化标记物过早翻译。总的来说，我们的多组学方法提出了新颖的转录后调节机制，对于皮层发育的准确性至关重要。©2023年，Sidhaye、Trepte等人。

During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the posttranscriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using human telencephalic brain organoids grown using a dual reporter cell line to isolate neural progenitors and neurons and performed cell class and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed modules of gene expression during human corticogenesis. Investigation of one such module uncovered mTOR-mediated regulation of translation of the 5'TOP element-enriched translation machinery in early progenitor cells. We show that in early progenitors partial inhibition of the translation of ribosomal genes prevents precocious translation of differentiation markers. Overall, our multiomics approach proposes novel posttranscriptional regulatory mechanisms crucial for the fidelity of cortical development.© 2023, Sidhaye, Trepte et al.