Molecular and cellular dynamics of the developing human neocortex

作者：Li Wang, Cheng Wang, Juan Moriano, Songcang Chen, Guolong Zuo, Arantxa Cebrián‐Silla, Shaobo Zhang, Tanzila Mukhtar, Shaohui Wang, Mengyi Song, Lilian Gomes de Oliveira, Qiuli Bi, Jonathan J. Augustin, Xinxin Ge, Mercedes F. Paredes, Eric J. Huang, Arturo Álvarez-Buylla, Xin Duan, Jingjing Li, Arnold R. Kriegstein · 发表于：Nature · 年份：2025 · DOI：10.1038/s41586-024-08351-7 · 被引用次数：140 · 研究领域：Single-cell and spatial transcriptomics、Epigenetics and DNA Methylation、MicroRNA in disease regulation

. Here we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and the primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence. In parallel, we performed spatial transcriptomic analysis on a subset of the samples to illustrate spatial organization and intercellular communication. This atlas enables us to catalogue cell-type-specific, age-specific and area-specific gene regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification and lineage-tracing experiments, we have untangled the complex lineage relationships among progenitor subtypes during the neurogenesis-to-gliogenesis transition. We identified a tripotential intermediate progenitor subtype-tripotential intermediate progenitor cells (Tri-IPCs)-that is responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells and astrocytes. Notably, most glioblastoma cells resemble Tri-IPCs at the transcriptomic level, suggesting that cancer cells hijack developmental processes to enhance growth and heterogeneity. Furthermore, by integrating our atlas data with large-scale genome-wide association study data, we created a disease-risk map highlighting enriched risk associated with autism spectrum disorder in second-trimester intratelencephalic neurons. Our study sheds light on the ...