031 Corneal epithelium basal cells can activate epidermal genetic programs by reverting first to hair stem cells

C. Ferraris1, G. Chevalier1, B. Favier1, C.A.B. Jahoda2 and D. Dhouailly1 Biologie Différenciation Epithéliale, UMR CNRS 5538, Institut A. Bonniot, Université J. Fourier, Grenoble, Fr1, Dept. of Biological Sciences, University of Durham, U.K.2

The capacity of the epithelial component of rabbit adult central cornea to follow an alternative differentiation pathway was investigated by associating it with a mouse embryonic dermis from a hairforming region. In the dermal-epithelial recombination experiments presented, because the nuclei of cells from these two components belong to two different species, they are easily recognizable : Hoechst staining allows easy discrimination of mouse and rabbit cell nuclei. Adult corneal epithelium, under the influence of embryonic skin dermis, undergoes a transition to an epidermal-type phenotype and produces hair follicles, corresponding to the regional identity of the dermis. The first stage of the transformation process appears to be the restoration of a more primitive limbal cell-like phenotype from amongst a TA cell population, which express corneal-type keratins, as shown by the use of a monoclonal antibody specific for K12. The second stage is the formation of hair buds, which can be considered to contain potential stem cells, the stem cell niche becoming subsequently progressively limited to the bulge region of the hair follicle. The third stage is the formation of an epidermis, characterized by the expression of epidermal-type keratins and the formation of a granular layer. The first epidermal cells expressing K10 always appeared at the top of the developing hair follicles. We thus confirm that follicles may be the primary source for epidermal homeostasis. Finally, the corneal layers which remains at the top of the new formed epidermis are progressively shedded. Our results provide the first indication that a distinct transient amplifying cell population can be reprogrammed, and they imply that they do so by reverting to a stem-like condition. They also show the equivalence of corneal epithelium and epidermal stem cells, which is perhaps a consequence of their common embryological origin.