A human embryonic stem cell-based model of trophoblast formation

Abstract

An efficient model of directing human embryonic stem cells (hESCs) to differentiate into the trophoblast lineage is established, the embryob s cellular contribution to the placenta. This rapid and uniform differentiation process is induced by the combined treatment of a specific fibroblast growth factor receptor (FGFR) inhibitor and bone morphogenetic protein 4 (BMP4). This thesis presents the details of this method for directing hESC towards trophoblast differentiation, the molecular changes that occur during this differentiation process, the commitment time point determination at which point the cells can no longer revert back to the hESC phenotype, the immediate targets of both the two signaling pathways and finally the convergence between fibroblast growth factor (FGF) signaling and BMP signaling during trophectoderm differentiation. In addition, the model, with its robust and uniform differentiated from the hESC, is unique in its utility to understand the molecular mechanisms involved in the loss of totipotency.