Current understanding in deciphering trophoblast cell differentiation during human placentation

The placenta is a unique organ that forms during gestation and supports fetus survival and communication with the mother. However, of such an essential organ for a successful pregnancy, our knowledge is limited. New progress has been made for human placenta study in recent years. We herein summarize the current understanding of human placental trophoblast differentiation and the molecules that govern trophoblast cell lineage specification. More importantly, the powerful tools for placental studies are also described such as human trophoblast stem cells, 3-dimensional (3D) trophoblast organoids, engineering-based placental devices, and single-cell RNA sequencing. These advances have brought us new insights into placental development and provided multiple investigation strategies for deciphering molecular mechanisms.