ABSTRACT

The derivation over a decade ago of cell lines from rhesus blastocyst stage in-vivo-produced embryos with many properties of embryonic stem cells (ESCs)1 paved the way for the derivation of similar cell lines from human in-vitro fertilization (IVF)- derived embryos.2 Strictly speaking, these lines have not yet been shown to fulfill all criteria of ESCs as derived from mouse (e.g. contribution to in-vivo organogenesis in chimeric embryos); however, they will be referred to as human ESCs as has become the convention. While these advances have generated substantial and deserved enthusiasm regarding the therapeutic potential of human embryo-derived cells, the significance of these cells for basic research into the fundamental processes of early human development is equally compelling. It was demonstrated early on that both rhesus and human cell lines shared a novel property not readily demonstrated with mouse ESCs: namely, the spontaneous (if perhaps inefficient) differentiation to cells of the trophoblast lineage. Several diverse paradigms have been developed that amplify this property of human ESCs. In this chapter, these paradigms will be summarized, the potential phenotype of the differentiated trophoblasts will be discussed and their significance for understanding the specification of the trophoblast lineage as well as the mechanisms by which the distinct trophoblast compartments within the

placenta are formed during development will be presented.