Using human pluripotent stem cells to dissect trophoblast development

In 2021, we showed that naive human pluripotent stem cells (PSCs) can differentiate into trophoblasts via trophectoderm (TE)-like cells. Since TE is a pre-implantation stage of trophoblasts constituting blastocysts, naive human PSCs are an invaluable tool for understanding the entire process of trophoblast development. It has been reported for many years that primed human PSCs can also differentiate into the trophoblast lineage. The in vitro differentiation of naive and primed human PSCs hints at the possibility that human pre- and even post-implantation epiblasts retain the differentiation potential into the trophoblast lineages in vivo. Here, we review the in vitro specification of trophoblasts from human PSCs. Moreover, we discuss the different trophoblast differentiation pathways from naive and primed PSCs.