Epithelial cells are continuously sloughed into the environment and replaced by similar cells from underneath. This coordinated homeostasis is maintained by a subpopulation of keratinocyte stem cells with high proliferative potential, located at the basal layer of the epidermis and thought to remain in the tissue for life. Identifying and isolating epidermal stem cells has proven difficult, and the lack of a widely accepted method has hampered their potential for use in tissue engineering, wound repair, gene therapy, and as cell therapy agents. In the October 15 Journal of Cell Science, Hong Wan and colleagues at the Guy's, King's and St. Thomas' School of Medicine report a novel strategy for the isolation of epidermal stem cells that combines a previously proposed marker with selection for low levels of expression of a surface protein (Journal of Cell Science, 116:4239-4248, October 15, 2003).

As keratinocytes mature and migrate from basal into suprabasal layers of skin, the number of desmosomes—specialized intercellular junctions characteristic of epithelial cells—increases. Hypothesizing that desmosomes could be sparse in epidermal stem cells, Wan et al. checked the expression profiles of several desmosomal proteins, such as desmogleins and desmoplakin, in both in vivo and cultured epidermal basal keratinocytes from human skin. They observed that clusters of palm keratinocytes that had very low cell surface expression of desmosomal proteins, in particular desmoglein3 (Dsg3), exhibited features expected for epidermal stem cells, such as high clonogenicity, colony-forming efficiency, and enhanced proliferative potential. They also observed that cells that express high levels of the protein β1 integrin—a well characterized positive cell surface marker for epidermal stem cells—have low levels of desmosomal proteins. In addition, the authors showed that combining the two surface markers of β1 integrin–bright and Dsg3-dull expression to sort keratinocytes considerably enriched the putative keratinocyte stem cell population.

"Our findings provide a novel strategy for the improved purification of adult putative epidermal stem/progenitor cells that could pave the way for further studies in stem cell and desmosome biology, and also have implications for the development of new keratinocyte stem cell-mediated clinical treatments," conclude the authors.