The trophoblast cell lineage is the first cell type to be specified during mammalian development – as the trophectoderm layer in the blastocyst – and is fated to form the epithelial cell compartment of the placenta (Cross et al. 1994, Rossant 1995). Trophoblast cells can be derived from blastocysts, at least in mice, that show properties expected of trophoblast stem (TS) cells in that they can differentiate into a range of differentiated trophoblast cell subtypes both in vitro and in vivo (Tanaka et al. 1998, Hughes et al. 2004). The trophoblast cell lineage is relatively simple in mice, in that TS cells differentiate into only four major differentiated cell types: trophoblast giant cells, spongiotrophoblast, glycogen trophoblast cells and syncytiotrophoblast (Cross et al. 2003) (Fig 1.1). Considerable progress has been made in the last few years in defining the molecular mechanisms that regulate the maintenance of the stem cell fate as well as the formation of the alternative differentiated cell types. This review focuses on the key transcription factors that specify trophoblast cell fates and the emerging evidence as to how signalling pathways interact with these transcription factors ultimately to regulate alternative cell fate decisions.

Trophoblast stem cells

Trophoblast stem cell lines can be derived from mice by culturing blastocysts or dissected extraembryonic ectoderm (chorionic trophoblast) in the presence of fibroblast growth factor (FGF)4 and feeder-cell conditioned medium (Tanaka et al. 1998).