出生后人类和猕猴前额叶皮层发育的单细胞时空转录组学和染色质可及性分析，这一成果由北京师范大学吴倩课题组经过不懈努力而取得。这一研究成果于2025年12月11日发表在国际顶尖学术期刊《自然—神经科学》上。

在这项研究中，该团队在单细胞分辨率下建立了人类和猕猴出生后PFC发育的基因表达、染色质可及性和空间转录组学的比较库。综合分析概述了不同细胞类型的物种特异性动态轨迹，突出了突触发生、突触修剪和胶质瘤发生等过程的关键窗口和基因调控网络。课题组确定了与猕猴相比，人类PFC发育延长的调控相关性。与猕猴相比，人类的神经胶质祖细胞具有更高的增殖能力，这与不同的基因表达谱有关。

此外，研究人员发现了最易受神经发育和神经精神疾病影响的细胞类型和谱系，重点关注具有人类特异性表达特征的转录因子。总之，他们的发现揭示了人类特异性调节程序通过协调神经元和神经胶质发育来延长出生后皮层成熟，这对认知和神经发育障碍具有启示意义。

据介绍，揭示人类前额叶皮层（PFC）发育的细胞和分子特征对于理解人类的认知能力和对神经和神经精神疾病的脆弱性至关重要。

附：英文原文

Title: Single-cell spatiotemporal transcriptomic and chromatin accessibility profiling in developing postnatal human and macaque prefrontal cortex

Author: Zhang, Jiyao, Li, Mayuqing, Wang, Mengdi, Sun, Yu, Yin, Chonghai, Yang, Shaotong, Wang, Bosong, Liu, Zeyuan, Wang, Wei, Liu, Min, Zhao, Yuqing, Zhou, Xin, Cai, Lixin, Zhong, Suijuan, Wang, Xiaoqun, Wu, Qian

Issue&Volume: 2025-12-11

Abstract: Unraveling the cellular and molecular characteristics of human prefrontal cortex (PFC) development is crucial for understanding human cognitive abilities and vulnerability to neurological and neuropsychiatric disorders. Here, in this study, we created a comparative repository for gene expression, chromatin accessibility and spatial transcriptomics of human and macaque postnatal PFC development at single-cell resolution. Integrative analyses outlined species-specific dynamic trajectories of different cell types, highlighting key windows and gene regulatory networks for processes such as synaptogenesis, synaptic pruning and gliogenesis. We identified regulatory correlates of the prolonged development of human PFC relative to macaques. Glial progenitors showed higher proliferation capability in humans compared to macaques, associated with distinct gene expression profiles. Furthermore, we uncovered cell types and lineages most susceptible to neurodevelopmental and neuropsychiatric disorders, focusing on transcription factors with human-specific expression features. In summary, our discoveries shed light on human-specific regulatory programs extending postnatal cortical maturation through coordinated neuronal and glial development, with implications for cognition and neurodevelopmental disorders.

DOI: 10.1038/s41593-025-02150-7

Source: https://www.nature.com/articles/s41593-025-02150-7