Embryonic stem cells (ESCs) are pluripotent cells with great therapeutic potentials. The in vitro differentiation of ESC was designed by recapitulating embryogenesis. Significant progress has been made to improve the in vitro differentiation protocols by toning soluble maintenance factors. However, more robust methods for lineage-specific differentiation and maturation are still under development. Considering the complexity of in vivo embryogenesis environment, extracellular matrix (ECM) cues should be considered besides growth factor cues. ECM proteins bind to cells and act as ligands of integrin receptors on cell surfaces. Here, we summarize the role of the ECM and integrins in the formation of three germ layer progenies. Various ECM–integrin interactions were found, facilitating differentiation toward definitive endoderm, hepatocyte-like cells, pancreatic beta cells, early mesodermal progenitors, cardiomyocytes, neuroectoderm lineages, and epidermal cells, such as keratinocytes and melanocytes. In the future, ECM combinations for the optimal ESC differentiation environment will require substantial study.
Definitive endoderm is the cellular precursor to respiratory- and digestive-related organs such as lungs, stomach, liver, pancreas and intestine. Endodermal lineage cells derived from pluripotent stem cells (PSCs) in vitro are a potentially unlimited resource for regenerative medicine. These cells are useful tools for studying the physiology, pathogenesis and medical therapies involving these tissues, and great progress has been achieved in PSCs differentiation protocols. In this review, we will focus on the most common and/or advanced differentiation strategies currently used in generating endodermal lineage cells from PSCs. A brief discussion about the effect of early definitive endoderm differentiation on the final development products will follow.
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