法国巴黎文理研究大学Alexandre D. Baffet发现，细胞命运决定图谱揭示人类新皮层发育过程中大量绕过中间祖细胞的直接神经发生过程。2024年3月28日，《自然—细胞生物学》杂志在线发表了这项研究成果。

研究人员开发了一种半自动活体/固定相关成像方法，用于绘制早期胎儿组织和脑类器官中基底放射状胶质细胞的分裂模式图。通过对数百个分裂祖细胞的活体分析，研究人员发现基底放射状胶质细胞经历了大量的对称放大分裂和频繁的自耗性直接神经源性分裂，绕过了中间祖细胞。这些直接神经源性分裂在室管膜下区上部更为丰富。此外，研究人员还证明了自我更新子细胞中不对称的Notch激活，与基底纤维遗传无关。这些研究结果揭示了脑类器官中命运决定的显著保守性，支持了它们作为人类早期神经发生模型的价值。

据悉，人类新皮质经历了强烈的演化扩张，这主要归功于基底放射状胶质细胞这一祖细胞群体的增加。这些细胞负责产生多种类型的细胞，但单个祖细胞的连续细胞命运决定仍然未知。

附：英文原文

Title: A cell fate decision map reveals abundant direct neurogenesis bypassing intermediate progenitors in the human developing neocortex

Author: Coquand, Laure, Brunet Avalos, Clarisse, Mac, Anne-Sophie, Farcy, Sarah, Di Cicco, Amandine, Lampic, Marusa, Wimmer, Ryszard, Bessires, Betina, Attie-Bitach, Tania, Fraisier, Vincent, Sens, Pierre, Guimiot, Fabien, Brault, Jean-Baptiste, Baffet, Alexandre D.

Issue&Volume: 2024-03-28

Abstract: The human neocortex has undergone strong evolutionary expansion, largely due to an increased progenitor population, the basal radial glial cells. These cells are responsible for the production of a diversity of cell types, but the successive cell fate decisions taken by individual progenitors remain unknown. Here we developed a semi-automated live/fixed correlative imaging method to map basal radial glial cell division modes in early fetal tissue and cerebral organoids. Through the live analysis of hundreds of dividing progenitors, we show that basal radial glial cells undergo abundant symmetric amplifying divisions, and frequent self-consuming direct neurogenic divisions, bypassing intermediate progenitors. These direct neurogenic divisions are more abundant in the upper part of the subventricular zone. We furthermore demonstrate asymmetric Notch activation in the self-renewing daughter cells, independently of basal fibre inheritance. Our results reveal a remarkable conservation of fate decisions in cerebral organoids, supporting their value as models of early human neurogenesis.

DOI: 10.1038/s41556-024-01393-z

Source: https://www.nature.com/articles/s41556-024-01393-z