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

ABSTRACT: The human ocular surface comprises corneal and conjunctival epithelia separated by the limbus, a specialized niche that maintains corneal transparency through limbal stem and progenitor cells (LSCs). 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. This niche dependent epithelial plasticity provides a mechanistic explanation for conjunctivalization in LSCD and identifies KGF–FGFR2 signaling as a potential therapeutic target for corneal epithelium restoration. Together, these findings redefine the limbus as a dynamic progenitor niche with broad implications for stem cell biology and regenerative medicine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE319837 | GEO | 2026/08/10

REPOSITORIES: GEO

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

Project description:The human ocular surface comprises corneal and conjunctival epithelia separated by the limbus, a specialized niche that maintains corneal transparency through limbal stem and progenitor cells (LSCs). 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. This niche dependent epithelial plasticity provides a mechanistic explanation for conjunctivalization in LSCD and identifies KGF–FGFR2 signaling as a potential therapeutic target for corneal epithelium restoration. Together, these findings redefine the limbus as a dynamic progenitor niche with broad implications for stem cell biology and regenerative medicine.

2026-08-10 | GSE319836 | GEO

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