Niche-driven plasticity of bipotent basal epithelial cells in the human ocular surface [scRNA-seq]

LSC loss or dysfunction causes limbal stem cell deficiency (LSCD), characterized by conjunctivalization, neovascularization, chronic inflammation, and corneal scarring, leading to severe visual impairmen. LSCD may result from injury, autoimmune disease or genetic disorders, yet current treatmens, including limbal transplantation and ex vivo–expanded epithelial grafts, are limited by donor availability and variable long term efficacy.

Until now, the limbus has been regarded as a static boundary enforcing lineage segregation between corneal and conjunctival epithelia. Here, we show that the human limbus instead harbors bipotent basal epithelial progenitors that are transcriptionally more similar to conjunctival than corneal basal cells and whose fate is directed by local niche cues. Keratinocyte growth factor (KGF) signaling through FGFR2 promotes corneal epithelial differentiation, whereas epidermal growth factor (EGF) maintains conjunctival identity.