Wu Zhisheng, Wang Yiheng, Chen Wei-Wei, Sun Hua, Chen Xiaoyan, Li Xiaobo, Wang Zeshuai, Liang Weizheng, Wang Shuang-Yin, Luan Xuemei, Li Yijiang, Huang Shangjin, Liang Yuteng, Zhang Jiaqi, Chen Zhou-Feng, Wang Guanlin, Gao Yun, Liu Yanan, Wang Jun, Liu Zhen, Shi Peng, Liu Cirong, Lv Longbao, Hou Anli, Wu Chenglin, Yao Chen, Hong Zexuan, Dai Ji, Lu Zhonghua, Pan Fan, Chen Xin, Kettenmann Helmut, Amit Ido, Speakman John R, Chen Yun, Ginhoux Florent, Cui Rongfeng, Huang Tianwen, Li Hanjie
Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; Department of Immunology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; School of Chemistry and Chemical Engineering, Center of Interventional Radiology and Vascular Surgery, Nurturing Center of Jiangsu Province for State Laboratory of AI Imaging & Interventional Radiology, Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; College of Biological Sciences, China Agricultural University, Beijing, China.
Cell. 2025 Apr 17;188(8):2159-2174.e15. doi: 10.1016/j.cell.2025.02.007. Epub 2025 Apr 7.
Microglia, essential in the central nervous system (CNS), were historically considered absent from the peripheral nervous system (PNS). Here, we show a PNS-resident macrophage population that shares transcriptomic and epigenetic profiles as well as an ontogenetic trajectory with CNS microglia. This population (termed PNS microglia-like cells) enwraps the neuronal soma inside the satellite glial cell envelope, preferentially associates with larger neurons during PNS development, and is required for neuronal functions by regulating soma enlargement and axon growth. A phylogenetic survey of 24 vertebrates revealed an early origin of PNS microglia-like cells, whose presence is correlated with neuronal soma size (and body size) rather than evolutionary distance. Consistent with their requirement for soma enlargement, PNS microglia-like cells are maintained in vertebrates with large peripheral neuronal soma but absent when neurons evolve to have smaller soma. Our study thus reveals a PNS counterpart of CNS microglia that regulates neuronal soma size during both evolution and ontogeny.
小胶质细胞在中枢神经系统（CNS）中至关重要，历史上被认为在外周神经系统（PNS）中不存在。在此，我们展示了一种外周神经系统驻留巨噬细胞群体，其与中枢神经系统小胶质细胞具有共享的转录组和表观遗传特征以及个体发育轨迹。这一群体（称为外周神经系统小胶质样细胞）包裹卫星神经胶质细胞包膜内的神经元胞体，在周围神经系统发育过程中优先与较大的神经元相关联，并通过调节胞体增大和轴突生长来维持神经元功能。对24种脊椎动物的系统发育调查揭示了外周神经系统小胶质样细胞的早期起源，其存在与神经元胞体大小（和体型）相关，而非与进化距离相关。与它们对胞体增大的需求一致，外周神经系统小胶质样细胞在具有大型外周神经元胞体的脊椎动物中得以保留，但当神经元进化为具有较小胞体时则不存在。因此，我们的研究揭示了中枢神经系统小胶质细胞在外周神经系统中的对应物，其在进化和个体发育过程中均调节神经元胞体大小。
