瑞士日内瓦大学Denis Jabaudon研究小组近日取得一项新成果。经过不懈努力，他们提出了祖细胞代谢的区域差异决定了发育过程中大脑的生长。该研究于2025年4月28日发表于国际一流学术期刊《细胞》杂志上。
该课题组提供了单细胞分辨率的单母脑出生图谱（www.neurobirth.org），揭示了后脑神经发生是短暂的，局限于早期发育，而前脑神经发生是通过减少心室区祖细胞的消耗分裂而暂时维持的。该图谱还揭示了直接和间接神经发生的区域特异性模式。利用单细胞RNA测序，该课题组人员确定了进化上保守的细胞周期程序和代谢相关的分子途径，这些分子途径控制着增殖的区域时间窗口。
课题组研究人员在体内功能获得和功能丧失实验中发现，晚期新皮层富集的线粒体蛋白FAM210B是一个关键的调节因子。FAM210B延长线粒体并增加乳酸的产生，从而促进祖细胞的自复制分裂，最终使其后代的克隆大小更大。总之，这些发现表明，线粒体功能的时空异质性调节了大脑发育过程中区域祖细胞循环行为和相关克隆神经元的产生。
据介绍，与大脑的其他部分相比，哺乳动物的前脑特别大，但这种区域扩张背后的发育机制仍然知之甚少。
附：英文原文
Title: Regional differences in progenitor metabolism shape brain growth during development
Author: Natalia Baumann, Robin J. Wagener, Awais Javed, Eleonora Conti, Philipp Abe, Andrea Lopes, Roberto Sansevrino, Adrien Lavalley, Elia Magrinelli, Timea Szalai, Daniel Fuciec, Clothilde Ferreira, Sabine Fièvre, Andreane Fouassier, Davide D’Amico, Oliver Harschnitz, Denis Jabaudon
Issue&Volume: 2025-04-28
Abstract: Mammals have particularly large forebrains compared with other brain parts, yet the developmental mechanisms underlying this regional expansion remain poorly understood. Here, we provide a single-cell-resolution birthdate atlas of the mouse brain (www.neurobirth.org), which reveals that while hindbrain neurogenesis is transient and restricted to early development, forebrain neurogenesis is temporally sustained through reduced consumptive divisions of ventricular zone progenitors. This atlas additionally reveals region-specific patterns of direct and indirect neurogenesis. Using single-cell RNA sequencing, we identify evolutionarily conserved cell-cycle programs and metabolism-related molecular pathways that control regional temporal windows of proliferation. We identify the late neocortex-enriched mitochondrial protein FAM210B as a key regulator using in vivo gain- and loss-of-function experiments. FAM210B elongates mitochondria and increases lactate production, which promotes progenitor self-replicative divisions and, ultimately, the larger clonal size of their progeny. Together, these findings indicate that spatiotemporal heterogeneity in mitochondrial function regulates regional progenitor cycling behavior and associated clonal neuronal production during brain development.
DOI: 10.1016/j.cell.2025.04.003
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00405-2