2. Academic Validation
  3. Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution

Peripheral nervous system microglia-like cells regulate neuronal soma size throughout evolution

  • Cell. 2025 Apr 17;188(8):2159-2174.e15. doi: 10.1016/j.cell.2025.02.007.
Zhisheng Wu 1,  Yiheng Wang 2,  Wei-Wei Chen 3,  Hua Sun 4,  Xiaoyan Chen 5,  Xiaobo Li 2,  Zeshuai Wang 3,  Weizheng Liang 6,  Shuang-Yin Wang 7,  Xuemei Luan 8,  Yijiang Li 9,  Shangjin Huang 10,  Yuteng Liang 3,  Jiaqi Zhang 3,  Zhou-Feng Chen 11,  Guanlin Wang 12,  Yun Gao 13,  Yanan Liu 13,  Jun Wang 3,  Zhen Liu 14,  Peng Shi 14,  Cirong Liu 15,  Longbao Lv 9,  Anli Hou 16,  Chenglin Wu 10,  Chen Yao 17,  Zexuan Hong 18,  Ji Dai 18,  Zhonghua Lu 18,  Fan Pan 18,  Xin Chen 8,  Helmut Kettenmann 19,  Ido Amit 7,  John R Speakman 19,  Yun Chen 20,  Florent Ginhoux 21,  Rongfeng Cui 22,  Tianwen Huang 23,  Hanjie Li 24
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 4 Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; School of Life Sciences, Henan University, Henan, China.
  • 5 Maternal-Fetal Medicine Institute, Department of Obstetrics and Gynaecology, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, China.
  • 6 Hebei Provincial Key Laboratory of Systems Biology and Gene Regulation, Central Laboratory, The First Affiliated Hospital of Hebei North University, Zhangjiakou, China.
  • 7 Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • 8 State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
  • 9 National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
  • 10 Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
  • 11 Institute of Neurological and Psychiatric Disorders, Shenzhen Bay Laboratory, and Shenzhen Medical Academy of Research and Translation, Shenzhen, China.
  • 12 Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China; Shanghai Qi Zhi Institute, Shanghai, China.
  • 13 State Key Laboratory of Genetic Resources and Evolution, and Southwest Research Centre of Porcine Molecular Breeding and Translational Medicine in China, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
  • 14 Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China.
  • 15 Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
  • 16 Shenzhen Guangming District People's Hospital, Shenzhen, China.
  • 17 The First Affiliated Hospital of Shenzhen University/Shenzhen Second People's Hospital, Shenzhen, China.
  • 18 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 19 Shenzhen University of Advanced Technology, Shenzhen, China.
  • 20 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. Electronic address: chenyun@njmu.edu.cn.
  • 21 INSERM U1015, Gustave Roussy Cancer Campus, Villejuif 94800, France.
  • 22 School of Ecology & State Key Laboratory of Biocontrol, Sun Yat-sen University, Shenzhen, China; Southern Marine Science and Engineering Guangdong Laboratory, Zhuhai, China.
  • 23 CAS Key Laboratory of Brain Connectome and Manipulation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, The Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 24 Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China; Shenzhen University of Advanced Technology, Shenzhen, China. Electronic address: hj.li@siat.ac.cn.
PMID: 40199320 DOI: 10.1016/j.cell.2025.02.007
Abstract

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.

Keywords

PNS microglia; evolution; macrophage; microglia; microglia-like cell; microglial lineage; neuron development; neuronal soma size; peripheral microglia; peripheral nervous system.

Figures
Products