Development of a high-efficiency induction system for embryonic oral epithelium from human pluripotent stem cells

Embryonic oral epithelium is a multipotent, ectodermal tissue that gives rise to various organs, including salivary glands, tooth germs, taste buds, and anterior pituitary glands. Although oral epithelium is contiguous posteriorly with endodermal epithelium and anteriorly with surface ectoderm, it exhibits distinct gene expression profiles during development. However, the molecular mechanisms that govern fate specification between oral epithelium and surface ectoderm remain poorly understood. Here, we present a highly efficient protocol for the PITX2-positive oral epithelium induction from human induced pluripotent stem cells (hiPSCs) using a reporter system. Sonic Hedgehog (SHH) signaling activation is essential for the efficient PITX2-positive epithelial cell generation. The induced cells exhibited gene expression profiles resembling those of embryonic oral epithelium and formed epithelial spheres that replicated features of human oral epithelium. This study established a robust platform for investigating human oral epithelial development and provided a valuable foundation for organoid-based research on oral organs.