Monocytes deposit migrasomes to promote embryonic angiogenesis.

Pro-angiogenic factors are key regulators of angiogenesis. Here we report that highly migratory cells patrol the area of capillary formation in chick embryo chorioallantoic membrane. These cells deposit migrasomes on their migration tracks, creating migrasome-enriched areas. Single-cell sequencing identified these cells as monocytes. Depletion of monocytes impairs capillary formation. Quantitative mass spectrometry analysis reveals that monocyte migrasomes are enriched with pro-angiogenic factors. Purified migrasomes promote capillary formation and monocyte recruitment in vivo, and endothelial cell tube formation and monocyte chemotaxis in vitro. Knockdown or knockout of TSPAN4 reduces migrasome formation and impairs capillary formation and monocyte recruitment. Mechanistically, monocytes promote angiogenesis via VEGFA and CXCL12 in migrasomes. In summary, monocytes deposit migrasomes enriched in pro-angiogenic factors to promote angiogenesis.