Different functional regions of brain are fundamental for basic neurophysiological activities. However, the regional specification remains largely unexplored during human brain development. Here, by combining spatial transcriptomics (scStereo-seq) and scRNA-seq, we built a spatiotemporal developmental atlas of multiple human brain regions from 6–23 gestational weeks (GWs). We discovered that, around GW8, radial glia (RG) cells have displayed regional heterogeneity and specific spatial distribution. Interestingly, we found that the regional heterogeneity of RG subtypes contributed to the subsequent neuronal specification. Specifically, two diencephalon-specific subtypes gave rise to glutamatergic and GABAergic neurons, whereas subtypes in ventral midbrain were associated with the dopaminergic neurons. Similar GABAergic neuronal subtypes were shared between neocortex and diencephalon. Additionally, we revealed that cell-cell interactions between oligodendrocyte precursor cells and GABAergic neurons influenced and promoted neuronal development coupled with regional specification. Altogether, this study provides comprehensive insights into the regional specification in the developing human brain.

大脑的不同功能区域是基本神经生理活动的基础。然而，在人类大脑发育过程中，区域规范在很大程度上仍未得到探索。在这里，通过结合空间转录组学 (scStereo-seq) 和 scRNA-seq，我们构建了 6-23 妊娠周 (GW) 多个人脑区域的时空发育图谱。我们发现，在 GW8 左右，放射状胶质细胞（RG）表现出区域异质性和特定的空间分布。有趣的是，我们发现 RG 亚型的区域异质性有助于随后的神经元规范。具体来说，两种间脑特异性亚型产生谷氨酸能和 GABA 能神经元，而腹侧中脑的亚型与多巴胺能神经元相关。新皮质和间脑具有相似的 GABA 能神经元亚型。此外，我们发现少突胶质细胞前体细胞和 GABA 能神经元之间的细胞间相互作用影响并促进神经元发育以及区域规范。总而言之，这项研究提供了对人类大脑发育中区域规范的全面见解。