Organization of Stem Cells and Their Progeny in Human Epidermis

Abstract

Renewal of epidermis is achieved by an ordered replication of stem cells and transit amplifying cells followed by terminal differentiation. In mouse epidermis, renewal is organized around highly ordered structures termed epidermal proliferative units (EPU), each generated by a single stem cell. It has been difficult to apply these concepts to the human epidermis where the basal layer is undulating and the strata have variable thickness. For example, it is unclear whether stem cells in human epidermis are located at the base of rete ridges or overlying the tip of dermal papilla. Data are available to support both views. To gain a better understanding of EPU organization in human skin, we have genetically marked xenografts of human foreskin with a lentivirus encoding a fluorescent marker protein and have mapped labeled columns of cells over a 28-wk period. By following these columns to their origin in the epidermis we have been able to determine that stem cells are dispersed along the basal compartment. The widths of these columns do vary considerably, with the narrowest originating from cells located in the base of the rete ridge. These findings provide new insights into the dynamics of epidermal renewal in human glabrous skin.