| Directed differentiation of human embryonic stem (hES) cells and human induced pluripotent stem (hiPS) cells captures in vivo developmental pathways for specifying lineages in vitro. Thus far, derivation of endodermal lineages has focused predominantly on hepatocytes, pancreatic endocrine cells and intestinal cells. The ability to differentiate pluripotent cells into anterior foregut endoderm (AFE) derivatives would expand their utility for cell therapy and basic research to tissues important for immune function, such as the thymus; for metabolism, such as thyroid and parathyroid; and for respiratory function, such as trachea and lung. I find that dual inhibition of transforming growth factor (TGF)-β and bone morphogenic protein (BMP) signaling after specification of definitive endoderm from pluripotent cells results in a highly enriched AFE population that is competent to be patterned along dorsoventral and anteroposterior axes into parathyroid, thymic, and lung lineages. The application of these patterning paradigmsto DiGeorge Syndrome iPS (DGS) allows the examination of pharyngeal endoderm in the setting of human congenital disease and provides novel pathogenetic insight. Together, these findings highlight that the generation of AFE from pluripotent stem cells is a powerful tool for the advancement of basic and translational research. |
