Abstract
Conversion of trophectoderm (TE)-derived trophoblast stem cells (TSCs) from inner-cell-mass-derived embryonic stem cells (ESCs) in mice is difficult to achieve naturally. Here, we introduce a reliable and repeatable protocol to generate induced TSCs (iTSCs) from ESCs via a Tet-on system in vitro. The iTSCs show typical TSC properties and have the potential to differentiate into syncytiotrophoblast cells (STCs) and trophoblast giant cells (TGCs). This cell fate transition provides a general platform to robustly investigate the mechanisms underlying TE specification. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2022).1.