The role of activin/nodal and Wnt signaling in endoderm formation.

Human embryonic stem cells (hESCs) are located within the inner cell mass of the preimplantation blastocysts. hESCs exhibit two important properties, the ability to generate exact copies of themselves, termed self-renewal, and pluripotency, the ability of stem cells to differentiate into every cell type of the embryo. This means that in theory it may be possible to generate an inexhaustible supply of primary human somatic cells in vitro which are suitable for application in regenerative medicine. Maintaining stem cell self-renewal and eliciting differentiation are dependent on the coordination of a number of signaling pathways which include members of the transforming growth factor beta (TGFβ) and Wnt families. The work in our laboratory has focused on the efficient generation of hepatocyte-like cells (HLCs) from hESCs and induced pluripotent stem cells (iPSCs). In order to mimic signaling during primitive streak and endoderm development, we have utilized TGFβ and Wnt signaling pathways in vitro. This has resulted in the generation of homogeneous populations of HLCs exhibiting liver specific function. This chapter will focus on TGFβ and Wnt signaling pathways and their role in primitive streak, endoderm, and HLC development.