The Molecular Basis of Embryonic Stem Cell Self-Renewal

Abstract

Peri-implantation stage embryos are a source of pluripotent cells that can be cultured indefinitely in vitro as a stable, self-renewing population. By definition, these cell populations have the capacity to differentiate into all cell types of the adult. Consequently, these cells are of special interest to developmental biologists and have significant potential in the area of cell replacement therapy. In this chapter we discuss the hallmarks of pluripotent cells derived from murine and human embryos and compare signaling pathways and transcription factor networks required for the self-renewing, pluripotent state. Maintenance of pluripotent cells derived from murine and human embryos requires different culture conditions for their in vitro maintenance, indicative of distinct differences at the molecular level and developmental nonequivalence. This chapter will evaluate the literature in terms of what is critical, from a signal transduction perspective, for maintenance of pluripotency and will highlight common themes that exist between embryonically derived stem cell populations, Recent findings describing epiblast stem cells (EpiScs), a self-renewing pluripotent cell type derived from post-implantation stage embryos, will be discussed with respect to embryonic stem cells and primitive ectoderm. EpiScs seem to be more closely related to hESCs than mESCs, posing some interesting questions as to the developmental equivalence of hESCs and mESCs. Finally, the new revolution of reprogramming from a differentiated state to an induced pluripotent stem (iPS) cell state will be discussed in relation to what we know about self-renewal regulatory networks and how this technology promises to revolutionize stem cell-based regenerative therapy.