Abstract
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 etv2ci32Gt 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 etv2ci32Gt; 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.
Highlights
Cell fate decisions involved in vascular and hematopoietic embryonic development are still poorly understood
While it is challenging to study early cardiovascular development in mammalian embryos, the zebrafish has emerged as an advantageous model system to study early cell fate decisions during embryogenesis
Etv[2] is expressed in vascular endothelial progenitor cells, as well as early myeloid and erythroid progenitors, and its expression is downregulated after cells undergo hematopoietic and vascular differentiation[5,6]
Summary
Cell fate decisions involved in vascular and hematopoietic embryonic development are still poorly understood. The lateral plate mesoderm (LPM) gives rise to multiple different cell lineages which include vascular endothelial cells, hematopoietic lineages and cardiomyocytes[1,2]. The specification of these lineages occurs in parallel to the specification of adjacent skeletal muscle progenitors which are thought to originate in the somites from different progenitors than the LPM lineages[3]. We and others have previously identified an ETS transcription factor Etv2/Etsrp which is one of the earliest markers of vascular and hematopoietic progenitor cells and functions as a key regulator of vascular and hematopoietic development in multiple vertebrates including mouse and zebrafish[5,6,7]. The fate decisions of LPM-derived cells are still poorly understood
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