Masatoshi Ohgushi

Summery: Human primed embryonic stem cells (pESCs) are known to be converted to cells with several trophoblast properties, but it has remained controversial whether this phenomenon represents the inherent differentiation competence of human pESCs to trophoblast lineages. In this study, we report that chemical blockage of ACTIVIN/NODAL and FGF signals is sufficient to steer human pESCs into GATA3-expressing cells that give rise to hormone-producing syncytia analogous to syncytiotrophoblasts of the post-implantation stage of the human embryo. Taking advantage of this system, we identified two distinct modes of cell-autonomous genetic programs and their coordinated actions to initiate the differentiation. We also found a transient population reminiscent of nascent amnion and then a spontaneous branch of differentiation trajectory leading to syncytiotrophoblast-like syncytial cells. These results provide insights into the possible extraembryonic differentiation pathway that is unique in primate embryogenesis and is relevant to the trophoblast competence of human primed pluripotent stem cells.

Human pluripotent stem cells indefinitely proliferate and survive in culture while retaining genomic integrity, providing a unique opportunity to study human molecular biology. Here, we introduced an RNA interference-based protocol of inducible gene silencing in human embryonic stem cells, which has several advantages in handling simplicity/convenience, cost/time performance, and applicability. Using this method, we had succeeded to elucidate the isoform-unique roles of Rho-family small GTPases in human embryonic stem cells.