Objective    To induce the dedifferentiation of human epidermal cells in vivo for the signaling pathways involved in the process.     Methods    The epidermis of human foreskin which was obtained with informed consent and approval of the Ethics Committee of our hospital was isolated from dermis by digestion with protease

and the cells in the stratum basale of the epidermis as well as stem cells were eliminated by repeated adhesion to collagen type Ⅳ. After being labeled with DAPI

the treated ultrathin epidermal

sheets were transplanted under the fresh full-thickness skin wounds about 1 cm in diameter on the back of athymic BALB/c nude mice. The transplanted sheets were harvested from the recipient at day 3

5 and 7 after xenotransplantation. Immunohistochemical assay

Western blot analysis and RT-PCR were used to determine the changes of cell phenotypes and ERK signaling pathway of the xenografts.     Results    CK19

β1 integrin

p63 and Oct4 positive cells were found in a single layer in stratum basal of the full-thickness epidermis

but were undetectable in ultrathin epidermal sheets before grafting. Most of the ultrathin epidermal sheets grew well in a soft and ruddy appearance after transplantation and the total survival rate was 86.3%. Immunological examinations showed that a certain number of cells were positive to CK19

β

1

integrin

p63 and Oct4 in spinous and granular layers after transplantation and that ERK/MAPK pathway was involved in the reversion process.     Conclusion    The differentiating epidermal cells could reverse to stem cell-like cells

and the process might be associated with the regulation of ERK/MAPK signaling pathway.