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  • br Therapeutic potential of stem

    2018-10-20


    Therapeutic potential of stem cell replacement therapies
    Conclusions
    Author contributions
    Introduction Intercellular adhesion plays important role in tissue architecture and morphogenesis by controlling the assembly of individual zip Supplier into the three-dimensional tissues (Cavallaro and Dejana, 2011). Cell–cell or cell–matrix interactions are mediated by cell adhesion molecules (CAMs) including cadherins, integrins, selectins and immunoglobulin-like CAMs, and regulate multiple aspects of cellular behavior including proliferation, differentiation, apoptosis, cell polarity (Cavallaro and Dejana, 2011; Niessen and Gumbiner, 2002), embryonic stem cell self-renewal and differentiation (Li et al., 2012) and overall, the maintenance of tissue integrity (Harris and Tepass, 2010). Cadherins represent one class of CAMs that mediate Ca2+ dependent homophilic interactions between cells, through formation of intercellular connections or otherwise known as adherens junctions (AJs). The most well studied cadherins are the classical vertebrate cadherins that have been named based on the tissue in which they are expressed. Neuronal cells mostly express N-cadherin (CDH2), while epithelial cells highly express E-cadherin (CDH1). Among the non-classical cadherins, VE-cadherin (CDH5) is expressed in endothelial cells and OB-cadherin (CDH11) is expressed in osteoblasts. However, the expression level of cadherins may vary during different cellular processes, especially those that involve transition from one cellular state to another. For example, it is well-established that the process of epithelial to mesenchymal transition (EMT) is characterized by augmented expression of CDH2 and CDH11 and diminished expression of CDH1 (Kimura et al., 1995; Zeisberg and Neilson, 2009; Tomita et al., 2000). Recent studies suggest that cadherin expression and cell–cell adhesion may also be critical in other transitions between cellular states such as lineage specification of stem cells or reprogramming of adult cells to a pluripotent state (Redmer et al., 2011; Alimperti et al., 2014a). Stem cell differentiation is affected by many soluble and insoluble signals in their local microenvironment. In addition to soluble growth factors, a number of elegant studies implicated cell-extracellular matrix (ECM) interactions and substrate mechanics in stem cell lineage commitment (Buxboim and Discher, 2010; Buxboim et al., 2010; Engler et al., 2006, 2007; Gao et al., 2010; McBeath et al., 2004; Treiser et al., 2010; Gilbert et al., 2010). However, the mechanical and biochemical signals originating from cell–cell adhesion remain relatively unexplored in this context. Recent studies implicated adherens junctions in the maintenance of embryonic stem cell self-renewal potential, cellular reprogramming, hematopoietic stem cell engraftment and mesenchymal stem cell (MSC) differentiation into the muscle (Redmer et al., 2011; Alimperti et al., 2014a; Hosokawa et al., 2010a). Here we provide a brief review on the role of cadherins, in particular CDH2 and CDH11, in development and stem cell fate decisions. This is a relatively nascent field of stem cell biology that has the potential to guide the development of novel strategies to control stem cell fate decisions as well as to inspire biomimetic design of nanomaterials for tissue engineering and regeneration.
    Adherens junctions: signal transduction and mechanosensing In general, classical cadherins including CDH2 and CDH11 have a common cytoplasmic domain and an ectodomain containing five tandem extracellular cadherin (EC) domains (Brasch et al., 2012) (Fig. 1). The EC domains contain Ca2+ binding sites in which three Ca2+ ions work as inter-domain linkers, stabilizing the ectodomain structure and protecting it from proteolysis (Boggon et al., 2002; Pokutta et al., 1994; Takeichi, 1991). The outermost EC1 domain regulates cadherin–cadherin interactions between adjacent cells, resulting in formation of adherens junctions between parallel opposing plasma membranes (Shapiro and Weis, 2009). Specifically, CDH2 and CDH11 are mostly expressed in mesenchymal type cells such as fibroblasts and cardiac cells and mediate intercellular adhesion between cells of the same type, e.g., myofibroblasts, or different cell types, e.g., between myofibroblasts and cardiac cells (Thompson et al., 2014).