Role of cell-cell adhesion complexes in embryonic stem cell biology

• Published in: Journal of cell science Vol. 127; no. Pt 12; pp. 2603 - 2613
• Main Authors: Pieters, Tim, van Roy, Frans
• Format: Journal Article
• Language: English
• Published: England 15-06-2014
• Subjects: Animals; Catenins - physiology; Cell Adhesion; Cell Adhesion Molecules - metabolism; Cell Differentiation; Cell Proliferation; Embryonic Stem Cells - physiology; Humans; Intercellular Junctions - physiology; Stemness; Junctional proteins; Somatic cell reprogramming; Epiblast stem cells; Teratomas; Embryonic stem cells; Chimeric mouse embryos; Catenins; Signaling pathways; Self-renewal; Induced pluripotent stem cells; Cadherins; Stem cell differentiation; Mesenchymal-to-epithelial transition; Pluripotency
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.146720

Pluripotent embryonic stem cells (ESCs) can self-renew or differentiate into any cell type within an organism. Here, we focus on the roles of cadherins and catenins - their cytoplasmic scaffold proteins - in the fate, maintenance and differentiation of mammalian ESCs. E-cadherin is a master stem cell regulator that is required for both mouse ESC (mESC) maintenance and differentiation. E-cadherin interacts with key components of the naive stemness pathway and ablating it prevents stem cells from forming well-differentiated teratomas or contributing to chimeric animals. In addition, depleting E-cadherin converts naive mouse ESCs into primed epiblast-like stem cells (EpiSCs). In line with this, a mesenchymal-to-epithelial transition (MET) occurs during reprogramming of somatic cells towards induced pluripotent stem cells (iPSCs), leading to downregulation of N-cadherin and acquisition of high E-cadherin levels. β-catenin exerts a dual function; it acts in cadherin-based adhesion and in WNT signaling and, although WNT signaling is important for stemness, the adhesive function of β-catenin might be crucial for maintaining the naive state of stem cells. In addition, evidence is rising that other junctional proteins are also important in ESC biology. Thus, precisely regulated levels and activities of several junctional proteins, in particular E-cadherin, safeguard naive pluripotency and are a prerequisite for complete somatic cell reprogramming.