4.8 Article

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

Journal

CELL
Volume 186, Issue 20, Pages 4454-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2023.08.019

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Macrophages in human development exhibit diversity and developmental dynamics. The study identifies the presence of microglia-like cells in the fetal epidermis and proangiogenic macrophages around fetal organs.
Macrophages are heterogeneous and play critical roles in development and disease, but their diversity, func-tion, 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 sub-types. 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 dy-namics of human macrophages and unravels their diverse functions during development.

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