An immune cell atlas reveals the dynamics of human macrophage specification during prenatal development
Zeshuai Wang1, Zhisheng Wu2, Hao Wang3
1Key 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.
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.
Insights
Human macrophages are diverse and crucial for development. This study maps their subtypes and functions during fetal development, revealing microglia-like cells in various tissues and their role in melanocyte development.
Area of Science:
- Developmental biology
- Immunology
- Single-cell genomics
Background:
- Macrophages are critical immune cells with diverse roles in health and disease.
- Understanding macrophage heterogeneity and development in humans is limited.
- Their precise functions and origins during human development require further elucidation.
Purpose of the Study:
- To create a comprehensive single-cell map of human macrophage development from early gestation to late fetal stages.
- To identify and characterize distinct macrophage subtypes and their functional roles.
- To investigate the origins and dynamics of human fetal macrophage populations.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) across 19 human fetal tissues (PCW 4-26).
- Spatial and differentiation trajectory analyses.
- Molecular and morphological characterization of identified macrophage populations.
Main Results:
- Identification of 15 distinct human macrophage subtypes.
- Discovery of a microglia-like population in fetal epidermis, testicle, and heart, interacting with neural crest cells.
- Characterization of a proangiogenic macrophage population found perivascularly across fetal organs.
- Demonstration of microglia-like cells as the predominant early immune cells in fetal epidermis.
Conclusions:
- Human macrophages exhibit significant heterogeneity during fetal development.
- Microglia-like cells play a role in modulating neural crest cell differentiation into melanocytes.
- Proangiogenic macrophages are likely yolk-sac-derived and contribute to vascular development.
- This study provides a foundational atlas for human fetal macrophage biology and function.
