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Cell fate decisions involved in vascular and hematopoietic embryonic development are still poorly understood. An ETS transcription factor Etv2 functions as an evolutionarily conserved master regulator of vasculogenesis. Here we report a single-cell transcriptomic analysis of hematovascular development in wild-type and  etv2  mutant zebrafish embryos. Distinct transcriptional signatures of different types of hematopoietic and vascular progenitors are identified using an  etv2   ci32Gt   gene trap line, in which the Gal4 transcriptional activator is integrated into the  etv2  gene locus. We observe a cell population with a skeletal muscle signature in  etv2- deficient embryos. We demonstrate that multiple  etv2   ci32Gt   ; UAS:GFP  cells differentiate as skeletal muscle cells instead of contributing to vasculature in  etv2 -deficient embryos. Wnt and FGF signaling promote the differentiation of these putative multipotent  etv2  progenitor cells into skeletal muscle cells. We conclude that  etv2  actively represses muscle differentiation in vascular progenitors, thus restricting these cells to a vascular endothelial fate.

Single-cell transcriptomic analysis identifies the conversion of zebrafish Etv2-deficient vascular progenitors into skeletal muscle