Derivation of Mouse Dome‐Shaped Trophoblast Stem Cells With Low Heterogeneity From Blastocysts

ABSTRACT Trophoblast stem cells (TSCs) have emerged as a valuable model for investigating placentation and related disorders. Despite their ability to be maintained over multiple passages without losing stemness, conventional TSCs are characterised by notorious heterogeneity and a spontaneous differentiation tendency. In this study, we established a type of mouse TSCs with dome‐shaped colonies (dTSCs). The dTSCs expressed canonical markers of conventional TSCs and exhibited relatively low levels of heterogeneity and spontaneous differentiation when cultured in conventional trophoblast stem cell medium. Additionally, dTSCs retained robust potential to differentiate into all trophoblast lineages in vitro, as well as the capacity to contribute to placental development in vivo. Furthermore, the functions of Foxo4 and Slc16a3 (MCT4) could be effectively explored in trophoblast development by using our established dTSCs. Collectively, our findings establish a type of high‐quality TSCs and define dTSCs as a promising and refined model for investigating trophoblast development.