CDH2 and CDH11 act as regulators of stem cell fate decisions

•The role of CDH11 and CDH2 in development and morphogenesis•The role of CDH2 and CDH11 during MSC lineage commitment•CDH11 mediated AJ formation promotes MSC differentiation into SMC.•Directing stem cell fate by controlling intracellular adhesion•Engineering cell–cell adhesion to direct stem cell fate decisions

Accumulating evidence suggests that the mechanical and biochemical signals originating from cell–cell adhesion are critical for stem cell lineage specification. In this review, we focus on the role of cadherin mediated signaling in development and stem cell differentiation, with emphasis on two well-known cadherins, cadherin-2 (CDH2) (N-cadherin) and cadherin-11 (CDH11) (OB-cadherin). We summarize the existing knowledge regarding the role of CDH2 and CDH11 during development and differentiation in vivo and in vitro. We also discuss engineering strategies to control stem cell fate decisions by fine-tuning the extent of cell–cell adhesion through surface chemistry and microtopology. These studies may be greatly facilitated by novel strategies that enable monitoring of stem cell specification in real time. We expect that better understanding of how intercellular adhesion signaling affects lineage specification may impact biomaterial and scaffold design to control stem cell fate decisions in three-dimensional context with potential implications for tissue engineering and regenerative medicine.