This technology includes a robust and highly efficient protocol that differentiates human pluripotent stem cells (hPSCs) into the developmental precursor of placental cells, the trophectoderm (TE), under chemically defined conditions. The in vitro generation of TE cells holds great promise for modeling diseases of the placenta, drug screening, and cell-based therapies. 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. Systematic testing of various cell culture conditions and simultaneous manipulation of specific cell signaling pathways has led to the ability to directly induce TE development within 10 days. These cells expressed typical TE markers such as GA T A3, KR T7, and CDX2.