Pax 6 Controls Neural Crest Potential of Limbal Niche Cells to Support Self-Renewal of Limbal Epithelial Stem Cells

On ocular surface, corneal epithelial stem cells (SC) reside in limbus between cornea and conjunctiva. Pax6, an evolutionally conserved transcription factor essential for eye development, is expressed in post-natal corneal and limbal epithelia progenitors (LEPC) but not in underlying stroma. Because...

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Bibliographic Details
Published in:Scientific reports 2019-07, Vol.9 (1), p.9763-13, Article 9763
Main Authors: Chen, Szu-Yu, Cheng, Anny M S, Zhang, Yuan, Zhu, Ying-Ting, He, Hua, Mahabole, Megha, Tseng, Scheffer C G
Format: Article
Language:English
Subjects:
Astrocytes
Biomarkers
Cell Differentiation - genetics
Cell Self Renewal - genetics
Cell self-renewal
Cells, Cultured
Conjunctiva
Cornea
Embryos
Epithelium, Corneal - cytology
Gene Expression
Genes, Reporter
Humans
Limbus Corneae - cytology
Neural crest
Neural Crest - cytology
Neural Crest - metabolism
Neural stem cells
Oligodendrocytes
Pax6 protein
PAX6 Transcription Factor - genetics
Phenotypes
Stem cells
Stem Cells - cytology
Stem Cells - metabolism
Stromal cells
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Summary:On ocular surface, corneal epithelial stem cells (SC) reside in limbus between cornea and conjunctiva. Pax6, an evolutionally conserved transcription factor essential for eye development, is expressed in post-natal corneal and limbal epithelia progenitors (LEPC) but not in underlying stroma. Because Pax6 is transiently expressed in developing corneal stroma and a subset of limbal and corneal stromal progenitors, we examined the role of Pax6 in limbal niche cells (LNC) in maintaining the phenotype of neural crest (NC) progenitors to support LEPC. Our results showed that nuclear Pax6 staining was found in freshly isolated LNC but not corneal stromal cells. Serial passaged LNC resulted in gradual loss of nuclear Pax6 (46 kDa) staining and neural crest progenitor status defined by the expression of embryonic SCs and NC markers, neurosphere formation, and differentiation into neurons, oligodendrocytes and astrocytes. Gain of function of 46 kDa Pax6 in late-passaged LNC resulted in nuclear Pax6 staining and promotion of the aforementioned NC progenitor status. In an in vitro reunion assay, early passaged LNC and late passaged LNC with overexpression of Pax6 inhibited the expression of corneal epithelial differentiation marker and promoted holoclone by LEPC. Therefore, expression of nuclear 46 kDa Pax6 in LNC plays an important developmental role in maintaining NC progenitor status to support self-renewal of corneal epithelial SCs in the limbal niche.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-45100-7