美国加利福尼亚大学Tomasz J. Nowakowski研究组宣布他们的最新研究提出了新生小鼠前脑的时空克隆结构。2026年9月30日出版的《自然》发表了这项成果。

哺乳动物前脑的数百种细胞类型在发育过程中如何从有限的前体细胞产生，仍很大程度上未知，迄今为止的研究绝大多数集中在大脑皮层。在此，为填补这一空白，研究人员对小鼠前脑的主要分区——皮层、海马、纹状体、丘脑和嗅球——应用了慢病毒条形码标记。他们利用空间转录组学将细胞图谱与其解剖分布对应起来，创建了新生小鼠前脑克隆细胞谱系关系图谱。研究人员揭示了腹侧和背侧中型多棘神经元生成中此前未被认识到的差异，以及晚期产生的多棘神经元、纹状体星形胶质细胞和嗅球神经元不同亚群之间未被探索的谱系关系。他们表明，具有广泛区域分散的GABA能（产生γ-氨基丁酸）神经元克隆富集了与神经发育障碍相关的基因。研究结果强调了一个发育原理：谷氨酸能神经元和星形胶质细胞克隆相关并保留在其起源区域内，而GABA能神经元与少突胶质细胞前体细胞克隆相关，但广泛分散于各脑区。总之，研究人员的发现将为哺乳动物前脑发育及其疾病研究提供基础参考。

附：英文原文

Title: Spatiotemporal clonal architecture of the newborn mouse forebrain

Author: Yuan, Guohua, Kunst, Michael, Steyert, Marilyn R., Keefe, Matthew G., Mathieu, Rmi, van Velthoven, Cindy T. J., McMillen, Delissa, Waters, Jack, Fukushima, Yasmin, Kazerounian, Adam, Alvarez-Buylla, Arturo, Zeng, Hongkui, Nowakowski, Tomasz J.

Issue&Volume: 2026-09-30

Abstract: How hundreds of cell types of the mammalian forebrain emerge from a limited set of progenitor cells during development remains largely unknown1,2,3, and studies so far have overwhelmingly focused on the cerebral cortex. Here, to fill this gap, we applied lentiviral barcoding across the major subdivisions of the mouse forebrain: cortex, hippocampus, striatum, thalamus and olfactory bulb. We registered cellular profiles to their anatomical distribution using spatial transcriptomics, creating an atlas of clonal cell lineage relationships across a newborn mouse forebrain. We uncover previously unrecognized differences in generation of ventral and dorsal medium spiny neurons, as well as unexplored lineage relationships between late-born medium spiny neurons, striatal astrocytes and distinct subpopulations of the olfactory bulb neurons. We show that clones of GABAergic (γ-aminobutyric acid-producing) neurons with broad regional dispersion are enriched for genes implicated in neurodevelopmental disorders. Our results highlight a developmental principle whereby glutamatergic neurons and astrocytes are clonally related and retained within their region of origin, whereas GABAergic neurons are clonally related to oligodendrocyte precursor cells but disperse extensively across brain regions. Together, our findings will serve as a foundational reference for studies of mammalian forebrain development and its disorders.

DOI: 10.1038/s41586-026-11064-8

Source: https://www.nature.com/articles/s41586-026-11064-8