Generation of functional conjunctival epithelium, including goblet cells, from human iPSCs

The conjunctival epithelium, which covers the sclera (the white of the eye) and lines the inside of the eyelids, is essential for mucin secretion and the establishment of a healthy tear film. Here, we describe human conjunctival development in a self-formed ectodermal autonomous multi-zone (SEAM) of cells that were derived from human-induced pluripotent stem cells (hiPSCs) and mimic whole-eye development. Our data indicate that epidermal growth factor (EGF) drives the generation of cells with a conjunctival epithelial lineage. We also show that individual conjunctival cells can be sorted and reconstituted by cultivation into a functional conjunctival epithelium that includes mucin-producing goblet cells. Keratinocyte growth factor (KGF), moreover, is necessary for the maturation of hiPSC-derived conjunctival epithelium—particularly the goblet cells—indicating key complementary roles of EGF and KGF in directing the differentiation and maturation, respectively, of the human conjunctival epithelium. [Display omitted] •Human iPSCs can give rise to cells of a conjunctival epithelial lineage•EGF signaling is required for conjunctival cells to develop from iPSCs•KGF is needed for the maturation of the iPSC-derived conjunctival epithelium•The iPSC-derived conjunctival epithelium contains mucin-producing goblet cells Nomi et al. generate conjunctival epithelial lineage cells from human iPSCs that have been expanded to form a two-dimensional, eye-like organoid. EGF and KGF work in conjunction to promote, respectively, the development and maturation of the iPSC-derived conjunctival epithelium, which contains mucin-producing goblet cells.