The Function of E-cadherin in ES Cell Pluripotency

Abstract

Stem cells have the potential to revolutionise medicine, providing treatment options for a wide range of diseases that currently lack a long term control strategy. In order for us to harness this potential, however, we need a thorough understanding of their self-renewal and differentiation capacities. Differentiation capacity, or ‘potency’, can be defined as the ability of a cell to give rise to every cell type within the developing embryo and its supporting tissues (totipotency), every tissue of the three germ layers: endoderm, ectoderm and mesoderm (pluripotency, Fig. 1.) or a restricted range of cell types (multipotency). The potency of a cell is dictated to some extent by the stage at which it is isolated from the embryo, which in turn affects its gene expression profile. For example, whereas embryonic stem (ES) cells are isolated from the inner cell mass (ICM) of the pre-implantation blastocyst, EpiS cells are derived from the later stage epiblast and exhibit significantly altered gene expression compared to mouse ES (mES) cells (Tesar et al., 2007). mES cells were first isolated from the ICM of the mouse blastocyst by two independent groups in 1981 (Evans and Kaufman, 1981; Martin, 1981) and have since been used as a model system in which to study mechanisms of development and disease. ES cells have also been isolated from other species including pig (Notarianni et al., 1990), rabbit (Graves and Moreadith, 1993) and chicken (Pain et al., 1996). In addition, pluripotent stem cells have been derived from cleavage-stage embryos, individual blastomeres (Chung et al., 2006; Klimanskaya et al., 2006; Wakayama et al., 2007), parthenogenic embryos (Lin et al., 2007; Mai et al., 2007; Revazova et al., 2007), trophectoderm (Tanaka et al., 1998) and extraembryonic endoderm (Kunath et al., 2005). Pioneering work in 1998 by Thomson and colleagues (Thomson et al.) resulted in the derivation of human embryonic stem (hES) cells from human blastocysts. Whilst mES and hES cells differ greatly in their gene expression profile (Tesar et al., 2007) and respond to distinct pluripotency-inducing signals (Daheron et al., 2004; Vallier et al., 2005), the core pluripotency regulatory network of Oct4, Sox2 and Nanog is conserved between the two species. Numerous studies have demonstrated the formation of an Oct4/Sox2 heterodimeric complex which is then responsible for activating the expression of a multitude of pluripotency-associated genes (Yuan et al., 1995; Botquin et al., 1998; Nishimoto et al., 1999). Many of the Oct4/Sox2 gene targets have been shown to be shared with Nanog in both mES (Loh et al., 2006) and hES cells (Boyer et al., 2005). Insight into this core