An immune cell atlas reveals the dynamics of human macrophage specification during prenatal development

  • Cell. 2023 Sep 6;S0092-8674(23)00908-X. doi: 10.1016/j.cell.2023.08.019.
Zeshuai Wang  1 ,  Zhisheng Wu  2 ,  Hao Wang  3 ,  Ruoqing Feng  4 ,  Guanlin Wang  5 ,  Muxi Li  6 ,  Shuang-Yin Wang  7 ,  Xiaoyan Chen  3 ,  Yiyi Su  1 ,  Jun Wang  4 ,  Weiwen Zhang  8 ,  Yuzhou Bao  9 ,  Zhenwei Lan  6 ,  Zhuo Song  10 ,  Yiheng Wang  11 ,  Xianyang Luo  12 ,  Lingyu Zhao  13 ,  Anli Hou  14 ,  Shuye Tian  15 ,  Hongliang Gao  14 ,  Wenbin Miao  14 ,  Yingyu Liu  3 ,  Huilin Wang  3 ,  Cui Yin  8 ,  Zhi-Liang Ji  6 ,  Mingqian Feng  16 ,  Hongkun Liu  17 ,  Lianghui Diao  18 ,  Ido Amit  7 ,  Yun Chen  19 ,  Yong Zeng  18 ,  Florent Ginhoux  20 ,  Xueqing Wu  21 ,  Yuanfang Zhu  22 ,  Hanjie Li  23
Affiliations
  • 1. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
  • 2. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; School of Chemistry and Chemical Engineering, Southeast University, Nanjing, China.
  • 3. Maternal Fetal Medicine Institute, Department of Obstetrics and Gynaecology, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, China.
  • 4. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
  • 5. Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Centre for Evolutionary Biology, Fudan University, Shanghai, China; Shanghai Qi Zhi Institute, Shanghai, China. Electronic address: [email protected].
  • 6. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
  • 7. Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
  • 8. Department of Gynaecology & Obstetrics, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China.
  • 9. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
  • 10. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Maternal Fetal Medicine Institute, Department of Obstetrics and Gynaecology, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, China.
  • 11. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; College of Biological Sciences, China Agricultural University, Beijing, China.
  • 12. The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 13. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Graduate School of Peking Union Medical College, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
  • 14. University of Chinese Academy of Sciences Shenzhen Hospital, Shenzhen, China.
  • 15. Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China.
  • 16. College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
  • 17. Jinxin Fertility Group Limited, Chengdu, China.
  • 18. Shenzhen Key Laboratory for Reproductive Immunology of Peri-Implantation, Shenzhen Zhongshan Institute for Reproduction and Genetics, Shenzhen Zhongshan Urology Hospital, Shenzhen, China.
  • 19. School of Chemistry and Chemical Engineering, Southeast University, Nanjing, China; Department of Immunology, Nanjing Medical University, Nanjing, China.
  • 20. Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; INSERM U1015, Gustave Roussy Cancer Campus, Villejuif 94800, France; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, Immunos, Singapore 138648, Singapore; Translational Immunology Institute, SingHealth Duke-NUS Academic Medical Centre, Singapore 169856, Singapore. Electronic address: [email protected].
  • 21. Department of Gynaecology & Obstetrics, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China. Electronic address: [email protected].
  • 22. Maternal Fetal Medicine Institute, Department of Obstetrics and Gynaecology, Shenzhen Baoan Women's and Children's Hospital, Jinan University, Shenzhen, China. Electronic address: [email protected].
  • 23. Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China. Electronic address: [email protected].
PMID: 37703875 DOI: 10.1016/j.cell.2023.08.019
Abstract

Macrophages are heterogeneous and play critical roles in development and disease, but their diversity, function, and specification remain inadequately understood during human development. We generated a single-cell RNA Sequencing map of the dynamics of human macrophage specification from PCW 4-26 across 19 tissues. We identified a microglia-like population and a proangiogenic population in 15 macrophage subtypes. Microglia-like cells, molecularly and morphologically similar to microglia in the CNS, are present in the fetal epidermis, testicle, and heart. They are the major immune population in the early epidermis, exhibit a polarized distribution along the dorsal-lateral-ventral axis, and interact with neural crest cells, modulating their differentiation along the melanocyte lineage. Through spatial and differentiation trajectory analysis, we also showed that proangiogenic macrophages are perivascular across fetal organs and likely yolk-sac-derived as microglia. Our study provides a comprehensive map of the heterogeneity and developmental dynamics of human macrophages and unravels their diverse functions during development.

Keywords
angiogenesis; developmental immunology; human immunology; immune cell atlas; macrophage; microglia; microglia-like cells; neural crest cells; perivascular macrophages; scRNA-seq.
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