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

ABSTRACT: During vertebrate embryogenesis, vascular endothelial cells originate in the lateral plate mesoderm (LPM) next to the progenitors of skeletal muscle. It is currently not clear what prevents vascular progenitors from responding to the adjacent signals that promote muscle development. An ETS transcription factor Etv2 functions as an evolutionarily conserved master regulator of vasculogenesis. Here we performed 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 were identified using an etv2ci32Gt gene trap line, in which Gal4 transcriptional activator has integrated into the etv2 gene locus. Unexpectedly, a cell population with the skeletal muscle signature was observed in etv2-deficient embryos. We demonstrate that multiple etv2ci32Gt; UAS:GFP cells migrate into the somites, elongate and differentiate as skeletal muscle cells instead of contributing to vasculature in etv2-deficient embryos. Wnt and FGF signaling promoted 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 locking these cells into vascular endothelial fate. We also identified the transcriptional signature of putative multipotent progenitors within the LPM that may give rise to vascular progenitor and skeletal muscle cells. Finally, we demonstrate that arterial progenitors co-express multiple arterial and venous markers during early stages of vasculogenesis, suggesting multi-potency of early vascular progenitors.These findings will be important in understanding the ontogeny of different mesodermal lineages and will help in designing in vitro differentiation strategies to generate vascular, muscle and other types of progenitors for therapeutic purposes.

ORGANISM(S): Danio rerio

PROVIDER: GSE142484 | GEO | 2020/03/10

REPOSITORIES: GEO