加州大学Aparna Bhaduri课题组近日取得一项新成果。经过不懈努力，他们报道了分子图谱的综合分析揭示驱动人类皮层发育细胞亚型规范的模块。这一研究成果发表在2025年4月21日出版的国际学术期刊《自然—神经科学》上。

通过对人类皮层发育（7个数据集）和成年（16个数据集）的平行荟萃分析，该研究团队生成了500多个基因共表达网络，可以描述皮层发育机制，主要集中在神经发生的高峰阶段。这些元模块在整个皮层发育过程中显示出动态的细胞亚型特异性，其中一些发育元模块显示出时空表达模式，暗示了细胞命运规范的潜在作用。该团队验证了这些模块在人类初级皮质组织中的表达。其中包括元模块20，一个在FEZF2⁺深层神经元中升高的模块，其中包括TSHZ3，一种与神经发育障碍相关的转录因子。人类皮层嵌合体实验证实FEZF2和TSHZ3都需要驱动模块20的活动和深层神经元规范，但通过不同的方式。这些研究证明了meta-atlases如何能够产生皮层命运规范的进一步机制分析。

据悉，人类大脑的发育需要产生不同的细胞类型，这是单细胞转录组学研究的一个过程。

附：英文原文

Title: Integrated analysis of molecular atlases unveils modules driving developmental cell subtype specification in the human cortex

Author: Nano, Patricia R., Fazzari, Elisa, Azizad, Daria, Martija, Antoni, Nguyen, Claudia V., Wang, Sean, Giang, Vanna, Kan, Ryan L., Yoo, Juyoun, Wick, Brittney, Haeussler, Maximilian, Bhaduri, Aparna

Issue&Volume: 2025-04-21

Abstract: Human brain development requires generating diverse cell types, a process explored by single-cell transcriptomics. Through parallel meta-analyses of the human cortex in development (seven datasets) and adulthood (16 datasets), we generated over 500 gene co-expression networks that can describe mechanisms of cortical development, centering on peak stages of neurogenesis. These meta-modules show dynamic cell subtype specificities throughout cortical development, with several developmental meta-modules displaying spatiotemporal expression patterns that allude to potential roles in cell fate specification. We validated the expression of these modules in primary human cortical tissues. These include meta-module 20, a module elevated in FEZF2+ deep layer neurons that includes TSHZ3, a transcription factor associated with neurodevelopmental disorders. Human cortical chimeroid experiments validated that both FEZF2 and TSHZ3 are required to drive module 20 activity and deep layer neuron specification but through distinct modalities. These studies demonstrate how meta-atlases can engender further mechanistic analyses of cortical fate specification.

DOI: 10.1038/s41593-025-01933-2

Source: https://www.nature.com/articles/s41593-025-01933-2