艾伦脑科学研究所曾红葵研究组取得一项新突破。他们揭示了端脑GABA能神经元的转录组学和空间组织。这一研究成果发表在2025年11月5日出版的国际学术期刊《自然》上。

在此，研究小组系统深入地分析了无主题端脑所有区域GABA能神经元类型的转录组学和空间组织及其发育起源。这项研究完成了对611423个年轻成人单细胞转录组和614569个单细胞转录组的主题化，这些转录组来自多个产前和产后发育时间点。研究组提出了成人远脑GABA能神经元的7类、52亚类、284超型和1051个细胞类型的分级组织，以及从胚胎第7天到出生后第14天的1688个细胞的相应发育分类。详细的图表工作揭示了非同寻常的复杂性，即细胞类型之间的关系反映了空间位置和发育起源。转录组学和发育相关的细胞类型经常在遥远和不同的大脑区域被发现，这表明远距离迁移和分散是几乎所有类型的远端脑GABA能神经元的共同特征。

此外，小组发现与基因表达梯度相关的相关细胞类型之间的离散和连续变异的不同空间维度。最后，该课题组人员发现皮层、纹状体和部分苍白质GABA能神经元在出生后广泛分化，而室间隔、视前和大多数苍白质GABA能神经元类型在胚胎期爆发，出生后分化有限。综上所述，端脑GABA能细胞类型的分类将为整个社会对细胞类型和电路的分子、结构和功能研究提供基础参考。

据悉，哺乳动物大脑的端脑包含多个区域和回路，这些区域和回路在各种脑功能中具有适应性和整合性作用。端脑GABA能神经元具有多样性；它们具有许多回路功能，这些神经元的功能障碍与各种脑疾病有关。

附：英文原文

Title: Transcriptomic and spatial organization of telencephalic GABAergic neurons

Author: van Velthoven, Cindy T. J., Gao, Yuan, Kunst, Michael, Lee, Changkyu, McMillen, Delissa, Chakka, Anish Bhaswanth, Casper, Tamara, Clark, Michael, Chakrabarty, Rushil, Daniel, Scott, Dolbeare, Tim, Ferrer, Rebecca, Gloe, Jessica, Goldy, Jeff, Guzman, Junitta, Halterman, Carliana, Ho, Windy, Huang, Mike J., James, Katelyn, McCue, Rachel, Nguy, Beagan, Cardenas, Trangthanh, Ronellenfitch, Kara, Thomas, Emma D., Torkelson, Amy, Pagan, Chelsea M., Kruse, Lauren, Dee, Nick, Ng, Lydia, Waters, Jack, Smith, Kimberly A., Tasic, Bosiljka, Yao, Zizhen, Zeng, Hongkui

Issue&Volume: 2025-11-05

Abstract: The telencephalon of the mammalian brain contains multiple regions and circuits that have adaptive and integrative roles in a variety of brain functions. GABAergic neurons in the telencephalon are diverse; they have many circuit functions, and dysfunction of these neurons has been implicated in various brain disorders1,2,3. Here we conducted a systematic and in-depth analysis of the transcriptomic and spatial organization of GABAergic neuronal types in all regions of the mouse telencephalon and their developmental origins. This was accomplished using 611,423 young adult single-cell transcriptomes and 614,569 single-cell transcriptomes collected from multiple prenatal and postnatal developmental timepoints. We present a hierarchically organized adult telencephalic GABAergic neuronal cell-type taxonomy of 7 classes, 52 subclasses, 284 supertypes and 1,051 clusters, as well as a corresponding developmental taxonomy of 1,688 clusters across ages from embryonic day 7 to postnatal day 14. Detailed charting efforts reveal extraordinary complexity whereby relationships among cell types reflect both spatial locations and developmental origins. Transcriptomically and developmentally related cell types are often found in distant and diverse brain regions, indicating that long-distance migration and dispersion is a common characteristic of nearly all classes of telencephalic GABAergic neurons. Moreover, we find various spatial dimensions of both discrete and continuous variation among related cell types that are correlated with gene expression gradients. Lastly, we find that cortical, striatal and some pallidal GABAergic neurons undergo extensive postnatal diversification, whereas septal, preoptic and most pallidal GABAergic neuronal types emerge in a burst during the embryonic stage with limited postnatal diversification. Overall, the telencephalic GABAergic cell-type taxonomy will serve as a foundational reference for molecular, structural and functional studies of cell types and circuits by the entire community.

DOI: 10.1038/s41586-025-09296-1

Source: https://www.nature.com/articles/s41586-025-09296-1