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F. Majo, A. Rochat, M. Nicolas, Y. Barrandon; Multipotency of Corneal and Conjunctival Stem Cells in Mammals . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3018.
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We found stem cells in the mouse and pig central cornea and conjunctiva. Using in vivo and in vitro experiments, we investigated the potential of differentiation of corneal and conjunctival epithelial stem cells.
Rosa26 mouse central cornea was grafted in the limbus area of a nude mouse after a conjunctival wound (n = 10). Rosa26 mouse conjunctiva was grafted in the peripheral cornea of a nude mouse after a total corneal wound (n = 10). Pig central corneal clones and pig conjunctival clones were plated and the differentiation of their progenies was investigated. Presence of corneal specific lineages was confirmed with K3 and presence of conjunctival specific lineages was confirmed with PAS coloration. Using RT–PCR and Nested–PCR, we analyzed specific gene expression patterns (Bmi1, Zfp145, p63, K12, Muc5ac, K4 and K19) of pig clones in cornea and conjunctiva.
Mouse central cornea can give rise to conjunctival lineages. Mouse conjunctiva can generate corneal lineages. Pig central corneal clones can generate pure goblet cells colonies whereas conjunctival clones are able to generate pure K3 colonies. Using RT–PCR and Nested–PCR, we demonstrated that corneal and conjunctival clones have the same ocular surface gene expression patterns.
Using in vivo and in vitro experiments, we demonstrated that corneal and conjunctival stem cells are multipotent, are able to give rise to the same lineages and have the same specific ocular surface molecular signature. According to these results, corneal and conjunctival stem cells are highly related or are identical. We propose a model where epithelial differentiation is regulated by the epithelio–mesenchymal interactions. In this model, the conjunctivalization of the central cornea could be explained by the switch of corneal stem cells differentiation. In this case, corneal stem cells give rise to conjunctival lineages because the epithelio–mesenchymal interactions involve conjunctival specific signals.
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