This technology includes in vitro-generated trophectoderm (TE) cells, which are ideal for modeling diseases of the placenta, drug screening, and cell-based therapies. The TE lineage which gives rise to placental cells during early human development. Derivation of definitive placental cells from human pluripotent stem cells in culture remains controversial and so far, placental cells can only be derived directly from primary placental tissue, which largely limits their access and study in the laboratory. This invention describes highly efficient TE differentiation, including cytotrophoblast and syncytiotrophoblast cells, by manipulating specific cell signaling pathways in chemically defined conditions.