Adult epidermal keratinocytes are endowed with pilosebaceous forming abilities

Pluristratified epithelia of adult vertebrate skin continuously regenerate from stem cells, and the question still arises as to whether those cells are committed to the production of only one cell lineage, or in contrast they conserve their embryonic pluripotentiality. In order to investigate the abilities of adult cultured as well as wound healing epidermis, heterospecific fibroblast-keratinocyte recombinations were performed, which allow unquestionable identification of the cells implicated in the structures that differentiate. Adult human cultured breast epidermal cells and full-thickness wound healing from human facial skin and foreskin were associated with either rabbit embryonic trichogenic dermis or cultured dermal papilla cells of adult rat, before grafting onto nude mice for two weeks to one month. In situ hybridization with a human specific sequence Alu probe labeled the human cells, whereas implanted rabbit or rat and host mouse cells were distinguished by the Hoechst staining of their nuclei. The results show that human adult cultured breast epidermal cells are able to form hair buds and to participate in hair follicle formation, while adult healing epidermis from a sparsely hairy skin as the human face or the dorsal skin of nude mouse, or even from a glabrous epidermis as the human foreskin, are able to differentiate pilosebaceous units. Although a follicular origin of the involved keratinocytes cannot be excluded in the three first cases, the formation of hair and sebaceous glands by foreskin keratinocytes of children 2 to 10 years-old establishes the cutaneous appendage ability of the interfollicular epidermal stem cells. The formation of interspecies mosaic follicles also highlights the fact that there must be a significant level of commonality in the interactive signaling molecules used by epithelial cells from different species.