Distinct contributions of Etv2+ and Flk1+ progenitors to endothelial, hematopoietic, and cardiac lineages

The ETS family transcription factor ETV2, VEGFA, and its receptor FLK1 are essential for hematopoietic, vascular, and cardiac development. Here, we combine dual Etv2 and Flk1 lineage tracing with molecular profiling to define how mesoderm progenitors are allocated to hematopoietic, endothelial, cardiomyocyte, and smooth muscle lineages. We demonstrate that hematopoietic, endothelial, and cardiac valves arise from dual Etv2⁺ and Flk1⁺ lineages and that Etv2⁺ and Flk1⁺ mesoderm contributing to the hemangiogenic fate is molecularly distinct from that generating muscle. Mechanistically, we show that ETV2 cooperates with the BAF chromatin remodeling complex to establish accessibility at ETV2 target loci. Loss of Baf155 expression reduces chromatin accessibility at ETV2 target loci and impairs hemangiogenic lineage specification. This work defines lineage relationships and the molecular circuitry underlying hemangiogenic specification during cardiovascular development.