ETV2 for endothelial fate specification

Directed induction of vascular regeneration and differentiation has significant clinical implications for the treatment of ischemic diseases and for the construction of functional, complex organoid models. The transcription factor ETS variant 2 (ETV2) has been identified in model organisms such as zebrafish and mice as a core regulator of embryonic angiogenesis, orchestrating vascular development by controlling endothelial cell (EC) differentiation. In recent years, in vitro studies have further revealed the multifaceted roles of ETV2. Beyond its essential function in embryonic vascular development, ETV2 can efficiently drive the differentiation or transdifferentiation of human pluripotent stem cells and somatic cells, such as fibroblasts, toward the endothelial lineage. These findings lay a theoretical basis for exploiting ETV2 in both vascular regenerative therapies and the in vitro generation of ECs. This review systematically summarizes the molecular mechanisms by which ETV2 governs endothelial fate specification during embryonic development, highlights current strategies for manipulating vascular cell differentiation in vitro, and discusses the major challenges associated with the translational application of ETV2-based cell engineering technologies.