Correct trophoblast development is essential for placenta function and embryogenesis. In humans, the early stages of this process can only be modelled in vitro using embryonic stem cells (ESCs); however, owing to the failure to identify the stepwise progression that occurs during differentiation, the identity of the resulting cells is not clear. Now, on , Mana Parast and colleagues narrow this gap by directly comparing various stages of in vitro trophoblast differentiation with in vivo cell types in the human placenta. The authors find that in vitro BMP4-driven trophoblast differentiation progresses through a p63+/KRT7+ stage that is akin to cytotrophoblast (CTB) cells in vivo. The CTB cells are the precursors of the terminally differentiated syncytiotrophoblast (STB) and extravillous trophoblast (EVT) cells. As expected, ESC-derived CTB-like cells can be differentiated further into functionally mature KLF4+ STB and HLA-G+ EVT cells. The authors propose that BMP4-driven differentiation of human ESCs is an accurate and informative model of human trophoblast development.
