Feng Xiangling, Gao Yingjie, Chu Fan, Shan Yuwen, Liu Meicheng, Wang Yaoyi, Zhu Ying, Lu Qing, Li Mingfeng
Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
National Demonstration Center for Experimental Basic Medical Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Nat Commun. 2025 Jan 15;16(1):672. doi: 10.1038/s41467-025-56058-8.
Cortical interneurons generated from ganglionic eminence via a long-distance journey of tangential migration display evident cellular and molecular differences across brain regions, which seeds the heterogeneous cortical circuitry in primates. However, whether such regional specifications in interneurons are intrinsically encoded or gained through interactions with the local milieu remains elusive. Here, we recruit 685,692 interneurons from cerebral cortex and subcortex including ganglionic eminence within the developing human and macaque species. Our integrative and comparative analyses reveal that less transcriptomic alteration is accompanied by interneuron migration within the ganglionic eminence subdivisions, in contrast to the dramatic changes observed in cortical tangential migration, which mostly characterize the transcriptomic specification for different destinations and for species divergence. Moreover, the in-depth survey of temporal regulation illustrates species differences in the developmental dynamics of cell types, e.g., the employment of CRH in primate interneurons during late-fetal stage distinguishes from their postnatal emergence in mice, and our entropy quantifications manifest the interneuron diversities gradually increase along the developmental ages in human and macaque cerebral cortices. Overall, our analyses depict the spatiotemporal features appended to cortical interneurons, providing a new proxy for understanding the relationship between cellular diversity and functional progression.
通过长距离切向迁移从神经节隆起产生的皮质中间神经元在不同脑区表现出明显的细胞和分子差异，这为灵长类动物中异质的皮质回路奠定了基础。然而，中间神经元的这种区域特异性是内在编码的还是通过与局部环境的相互作用获得的，仍然不清楚。在这里，我们从发育中的人类和猕猴物种的大脑皮质和皮质下区域（包括神经节隆起）中招募了685,692个中间神经元。我们的综合和比较分析表明，与在皮质切向迁移中观察到的剧烈变化相比，中间神经元在神经节隆起亚区内迁移时伴随的转录组变化较少，皮质切向迁移中的剧烈变化主要表征了不同目的地和物种差异的转录组特异性。此外，对时间调控的深入研究揭示了细胞类型发育动态中的物种差异，例如，灵长类动物中间神经元在胎儿后期对促肾上腺皮质激素释放激素的利用与小鼠出生后的情况不同，并且我们的熵量化表明，人类和猕猴大脑皮质中的中间神经元多样性随着发育年龄逐渐增加。总体而言，我们的分析描绘了附加在皮质中间神经元上的时空特征，为理解细胞多样性与功能进展之间的关系提供了一个新的切入点。
