A comparison of trophoblast lineage derivation in the mouse (upper) and human (lower). This diagram is based on that of Cross et al. . Trophoblast lineage cell types are illustrated in black letters, with the direction of differentiation shown in black arrows; other lineages are shown in gray. Key transcription factors that either support or drive differentiation are shown adjacent to the arrows. Most of these are discussed in the text. Attempts have been made to illustrate possible homology between the two species. Oct4 is expressed in the ICM both species. Mouse trophectoderm is only specified when Oct4 becomes down-regulated. As discussed in the text, Cdx2 and Eomes are required early in the mouse trophectoderm development. Mouse TS cells can be derived from blastocysts and early postimplantation trophoblasts and grow in the presence of FGF4. Removal of FGF4 from the TS cell culture causes them to differentiate into trophoblast giant cells and other trophoblast subtypes. Human ES cells are derived from blastocyst and maintained in the presence of bFGF. They are able to give rise to all cell types of the embryo but can also differentiate into trophoblast cells either spontaneously or in a directed manner when provided with BMP4. Id2 is expressed in both mouse chorionic trophoblast and human villous cytotrophoblast [11, 79], while Mash2 is expressed in murine spongiotrophoblast and in the cytotrophoblast columns of the human placenta [77, 80]. Hand1, is necessary for the formation of mouse giant cells but not for the specification of spongiotrophoblast and syncytiotropphoblast. By contrast, Mash2 (or Hash2 in the human), has the opposite effect to Hand1. In the giant cell lineage, Hand1 must be down-regulated for giant cells to form. The gene mSNA, which represses the transcription of genes that promote the transition from mitotic to endoreplicative cell cycles in mouse trophoblast , becomes down regulated during giant cell differentiation, but has not been studied in other species. Human extravillous cytotrophoblast may be the functional homolog of the rodent trophoblast giant cells, although expression of Hand1 has not been detected in human placental villi . On the other hand, expression of Gcm1 in mouse labyrinth  and human chorionic villi [77, 78] is consistent with structural homology of the tissues.