Proangiogenic Macrophage Development in Human Prenatal Stage: A Key Element in Maternal-Fetal Medicine Puzzle

Macrophages are a major immune cell type constituting the human innate immune system that is involved in various physiological processes, including tissue development, remodeling, homeostasis, and repair, which are essential to maintain the normal growth and development of embryos/fetuses. They exhibit a diverse range of phenotypes influenced by their cellular origin and the specific environments within different tissues. Additionally, there exist distinct macrophage subtypes that can be found in multiple organs. Our recent study published in Cell has provided a developmental atlas of the human prenatal immune system, which collected nearly 300,000 immune cells from 19 tissues spanning 18 gestational time points from postconceptional 4 to 26 weeks, using single-cell transcriptome sequencing analysis. This study has also provided new insights into the differentiation, spatial distribution, functional traits, and transcriptional regulation mechanisms of different macrophage subtypes during development, which have shed light on the intricate processes involved in macrophage development during the human prenatal stage. Additionally, we have also identified two new macrophage subtypes, with one of them being proangiogenic macrophages (PraMs), which possess the capability to promote angiogenesis. These PraM cells were found to be distributed across various tissues, indicating their importance in the development and maintenance of blood vessels during the prenatal stage. Understanding the role of prenatal PraMs in promoting angiogenesis and vasculogenesis in the fetus and placenta can help better comprehend the pathogenesis of adverse pregnancy outcomes. Furthermore, the investigation into the origins of PraMs from different sites highlights the importance of considering the heterogeneity of these cells. In conclusion, the study of prenatal PraMs emerges as a crucial piece of the puzzle and provides insights into the field of maternal-fetal medicine. It also offers promising directions for future research and interventions aimed at improving maternal and fetal health.