马克斯·普朗克生物智能研究所Christian Mayer小组在研究中取得进展。他们的最新研究提出了祖细胞能力的时间控制决定了小鼠gaba能神经元发育的成熟。该项研究成果发表在2025年7月8日出版的《自然—神经科学》上。

利用单细胞转录组学、染色质可及性分析、谱系追踪、出生测定、跨发育阶段移植和单主题胚胎的扰动测序，课题组人员研究了祖细胞能力如何影响这些神经元的成熟和分化。该研究组发现神经发生的时间进展决定了神经节隆起祖细胞的成熟能力，影响了它们的后代如何向成熟状态发展。相比之下，分化能力——被定义为祖细胞产生不同转录组特征的能力——在整个神经发生过程中保持不变。染色质重塑与由转录因子NFIB及其靶基因组成的调控模块一起影响了晚生神经元的成熟能力。这些发现揭示了转录程序和染色质可及性如何在神经发育过程中控制神经元成熟和GABA能神经元亚型的多样化。

研究人员表示，端脑的GABA能投射神经元和中间神经元的不同类型来源于被称为神经节隆起的腹侧生发带的祖细胞。

附：英文原文

Title: Temporal control of progenitor competence shapes maturation in GABAergic neuron development in mice

Author: Bright, Ann Rose, Kotlyarenko, Yana, Neuhaus, Florian, Rodrigues, Diana, Feng, Chao, Peters, Christian, Vitali, Ilaria, Dnmez, Elif, Myoga, Michael H., Dvoretskova, Elena, Mayer, Christian

Issue&Volume: 2025-07-08

Abstract: Diverse types of GABAergic projection neuron and interneurons of the telencephalon derive from progenitors in a ventral germinal zone called the ganglionic eminence. Using single-cell transcriptomics, chromatin accessibility profiling, lineage tracing, birthdating, transplantation across developmental stages and perturbation sequencing in mouse embryos, we investigated how progenitor competence influences the maturation and differentiation of these neurons. We found that the temporal progression of neurogenesis shapes maturation competence in ganglionic eminence progenitors, influencing how their progeny progress toward mature states. By contrast, differentiation competence—defined as the ability of progenitors to produce diverse transcriptomic identities—was maintained throughout neurogenesis. Chromatin remodeling, together with a regulatory module composed of the transcription factor NFIB and its target genes, influenced maturation competence in late-born neurons. These findings reveal how transcriptional programs and chromatin accessibility govern neuronal maturation and the diversification of GABAergic neuron subtypes during neurodevelopment.

DOI: 10.1038/s41593-025-01999-y

Source: https://www.nature.com/articles/s41593-025-01999-y