Protein Kinase C Mediated Extraembryonic Endoderm Differentiation of Human Embryonic Stem Cells

Unlike mouse embryonic stem (ES) cells, which are closely related to the inner cell mass, human ES cells appear to be more closely related to the later primitive ectoderm. For example, human ES cells and primitive ectoderm share a common epithelial morphology, growth factor requirements, and the potential to differentiate to all three embryonic germ layers. However, it has previously been shown that human ES cells can also differentiate to cells expressing markers of trophoblast, an extraembryonic lineage formed before the formation of primitive ectoderm. Here we show that phorbol ester 12-O-Tetradecanoylphorbol 13-acetate (TPA) causes human ES cells to undergo an epithelial mesenchymal transition and to differentiate into cells expressing markers of parietal endoderm, another extraembryonic lineage. We further confirmed that this differentiation is through the activation of PKC pathway and demonstrated that a particular PKC subtype, PKC-delta, is most responsible for this transition. This is a time course design. It includes 16 samples.