Abstract
Pluripotent stem cells have the capacity to generate all cell lineages, and substantial progress has been made in realizing this potential. One fascinating but as yet unrealized possibility is the differentiation of pluripotent stem cells into thymic epithelial cells. The thymus is a primary lymphoid organ essential for naïve T-cell generation. T cells play an important role in adaptive immunity, and their loss or dysfunction underlies in a wide range of autoimmune and infectious diseases. T cells are generated and selected through interaction with thymic epithelial cells, the functionally essential element of thymus. The ability to generate functional thymic epithelial cells from pluripotent stem cells would have applications in modeling human immune responses in mice, in tissue transplantation, and in modulating autoimmune and infectious disease.