Human embryonic stem cells as models for trophoblast differentiation

Trophectoderm is specified from pluripotent blastomeres at some time prior to blastocyst formation. Proliferating cytotrophoblast derived from trophectoderm is the forerunner of the entire trophoblast component of the mature human placenta, including extravillous cytotrophoblast and syncytiotrophoblast. Recently human embryonic stem cells (hESC) have been employed to study these events in an in vitro situation. Here we review some of the work in this emerging area of trophoblast biology. We concentrate primarily on a model in which colonies of hESC are exposed to BMP4 in stem cell growth medium lacking FGF2. Under both low (4%) and high (20%) O(2) conditions, differentiation proceeds unidirectionally towards trophoblast from the outside of the colonies inwards, with the progression fastest under high O(2). Immunohistochemical observations performed on whole colonies combined with microarray analysis of mRNA can be employed to track developmental transitions as they occur over time and in two-dimensional space as the cells respond to BMP4.