Investigative ophthalmology & visual science · 2026
PAX6 Deficiency Compromises the Ability of Limbal Epithelial Stem Cells to Properly Differentiate Into Mature Corneal Epithelial Cells.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Foroozandeh Parisa, Kaplan Nihal, Qi Xiaolin, Yang Wending, Chen Xiaoping, Lee Sun Kyong, Ren Ziyou, Lavker Robert M, Kume Tsutomu, Peng Han
Аннотация
PURPOSE: Aniridia, driven by PAX6 mutations, causes aniridia-associated keratopathy (AAK), a progressive condition linked to limbal stem cell deficiency. A major hurdle to developing targeted therapies for AAK is the incomplete understanding of the molecular abnormalities in affected corneas. To address this, we leveraged Pax6± (Pax6 het) mice, a model of AAK, and applied single-cell RNA sequencing (scRNA-seq) to profile the transcriptomic changes at a single-cell resolution.
METHODS: ScRNA-seq of corneal/limbal tissues of wild type (WT) and Pax6 het mice were conducted. Immunostaining was performed to examine the expression of specific markers for stem cells.
RESULTS: ScRNA-seq identified a quiescent limbal epithelial stem cell (LESC)-like cell cluster and an early transient amplifying cell (eTAC)-like cluster. An increase in the cell numbers in these two clusters in the Pax6 het mouse corneas was observed. Immunostaining detected a marked increase in markers for these two clusters including Tmem176b, Apoe, and Krt15 in the corneal epithelium of Pax6 het mice, suggesting an increase of these LESC/eTA-like cells into the corneal epithelium. The Pax6 deficiency inhibited the expression of genes involved in cell proliferation in the eTAC-like cluster as well as the expression of genes related to corneal epithelial cell fate and differentiation compared with WT mice.
CONCLUSIONS: Our single cell transcriptome of the limbus and cornea of Pax6 het mice indicates that AAK may be due to the increase of dysfunctional stem/eTACs with defects in committing to a corneal epithelial cell fate and differentiation.
METHODS: ScRNA-seq of corneal/limbal tissues of wild type (WT) and Pax6 het mice were conducted. Immunostaining was performed to examine the expression of specific markers for stem cells.
RESULTS: ScRNA-seq identified a quiescent limbal epithelial stem cell (LESC)-like cell cluster and an early transient amplifying cell (eTAC)-like cluster. An increase in the cell numbers in these two clusters in the Pax6 het mouse corneas was observed. Immunostaining detected a marked increase in markers for these two clusters including Tmem176b, Apoe, and Krt15 in the corneal epithelium of Pax6 het mice, suggesting an increase of these LESC/eTA-like cells into the corneal epithelium. The Pax6 deficiency inhibited the expression of genes involved in cell proliferation in the eTAC-like cluster as well as the expression of genes related to corneal epithelial cell fate and differentiation compared with WT mice.
CONCLUSIONS: Our single cell transcriptome of the limbus and cornea of Pax6 het mice indicates that AAK may be due to the increase of dysfunctional stem/eTACs with defects in committing to a corneal epithelial cell fate and differentiation.