Figure 2
(A) Diagrammatic representation of the differentiation pathway that cytotrophoblast stem cells undertake in vivo. These cells detach from the underlying uterine basement membrane and either fuse to form multinucleated syncytiotrophoblasts or columns of mononuclear cells that attach the conceptus to the uterine wall. A subset of these cells stops proliferating and differentiates into invasive cytotrophoblasts that breach and enlarge maternal blood vessels to generate an utero–placental circulation. The differentiation of proliferating cytotrophoblasts into invasive cytotrophoblasts is an O2-dependent process, with O2 levels increasing as cells migrate towards the maternal spiral arteries. (B) Placentation is regulated by changes in O2 availability. An E8.0 mouse embryo is shown to illustrate the O2 gradient generated during murine placentation. Similar to human placentae, the early murine placenta generates an O2 gradient where cells that migrate dorsally experience increasing O2 levels. Trophoblast stem cells adopt specific cell fates in the placenta when they encounter discrete O2 levels: low O2 enforces a spongiotrophoblast cell fate, whereas higher O2 levels enforce a giant cell fate.