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Rapid Differentiation of Multi-Zone Ocular Cells from Human Induced Pluripotent Stem Cells and Generation of Corneal Epithelial and Endothelial Cells.

Eye is a complex organ with a highly specialized tissue structure. The establishment of human pluripotent stem cells (hPSCs) has allowed the simulation of eye development in vitro. Most differentiation works of hPSC-derived ocular cells focus on a single, tissue-specific lineage, however, that faces difficulty in reflecting the complexity of eye development. Recently, the generation of a self-formed ectodermal autonomous multi-zone of ocular cells availably mimics the process of whole-eye development. In this study, we developed a rapid defined method to induce the differentiation of multi-zone ocular cells (MZOCs) from human induced pluripotent stem cells, which specifically experienced the key progenitor stages of anterior neuroectoderm and eye field stem cells by a 2.5-dimensional culture. These differentiated cell types spanned neural retina, retinal pigment epithelium, surface ectoderm, and neural crest and lens cells. In addition, the surface ectoderm zone of MZOCs could be mechanically isolated and induced into corneal epithelial cells, and the isolated neural crest zone could be directed into corneal endothelial cells. This in vitro differentiation process vividly mimics the development of vertebrate eye, and it provides a promising model for the study of ocular morphogenesis, as well as an ideal resource of seed cells for corneal regenerative medicine.