加州大学Tomasz J. Nowakowski研究团队揭示了发育中的人类皮质的谱系分辨图谱。该研究于2025年11月5日发表于国际一流学术期刊《自然》杂志上。

在这里，研究小组应用前瞻性谱系追踪来绘制人类神经干细胞和祖细胞分化的多样性，跨越发育窗口，包括人类原代组织中的神经发生和胶质瘤发生。通过分析6402个祖细胞的克隆输出，该研究团队创建了一个谱系分辨的人类皮质发育图谱。

在这里，研究组发现皮质祖细胞在妊娠中期从谷氨酸能神经发生转变为GABA能（涉及γ-氨基丁酸）神经发生，这与少突胶质细胞生成的开始一致。此外，该研究团队发现截断的放射状胶质细胞在人类皮层发育过程中长时间保持谷氨酸能神经发生的潜力。出乎意料的是，研究组发现来自截短的放射状胶质细胞的晚生谷氨酸能神经元表现出皮层深层神经元的分子特征，并可能有助于妊娠中期亚板区域的扩张。

据介绍，人类新皮层由多种细胞类型组成，这些细胞类型在发育过程中根据神经干细胞启动的空间和时间组织程序产生。尽管越来越多的研究已经捕获了单细胞沿分化和成熟轴的基因表达快照，但将单个祖细胞与特定神经元和神经胶质亚型联系起来的谱系关系的潜在图谱仍然未知，特别是在人类中。

附：英文原文

Title: Lineage-resolved atlas of the developing human cortex

Author: Keefe, Matthew G., Steyert, Marilyn R., Nowakowski, Tomasz J.

Issue&Volume: 2025-11-05

Abstract: The human neocortex is composed of diverse cell types1 that are generated during development according to spatially and temporally organized programmes initiated by neural stem cells2,3,4,5. Despite the growing number of studies that have captured snapshots of gene expression of single cells along the axis of differentiation and maturation, the underlying map of lineage relationships that link individual progenitor cells to specific subtypes of neurons and glia remains unknown, especially in humans. Here we applied prospective lineage tracing to map the manifold of human neural stem and progenitor cell differentiation across the developmental window encompassing neurogenesis and gliogenesis in human primary tissue. By profiling the clonal output of 6,402 progenitor cells, we created a lineage-resolved map of human cortical development. Here we show that cortical progenitors switch from glutamatergic to GABAergic (involving γ-aminobutyric acid) neurogenesis around midgestation, which coincides with an onset of oligodendrocyte generation. Additionally, we find that truncated radial glia maintain a glutamatergic neurogenic potential for a protracted period during human cortical development. Unexpectedly, we find that late-born glutamatergic neurons derived from truncated radial glia exhibit molecular features of deep cortical layer neurons and may contribute to the expansion of the subplate region during midgestation.

DOI: 10.1038/s41586-025-09033-8

Source: https://www.nature.com/articles/s41586-025-09033-8