Side population cells in human and mouse epidermis lack stem cell characteristics

Cells that exclude Hoechst 33342 have been found in many tissues, and common for these cells is a characteristic profile when analysed by flow fluorimetry (sp, side population). Since sp cells in some cases function as multipotent stem cells, we investigated whether the epidermis contains sp cells (Esp cells) and whether these cells were epidermal stem cells. We show that mouse and human epidermis contain sp cells, and, to identify the origin of these cells, we tested the expression of several marker genes. We find that Esp cells constitute a subpopulation of the alpha6 integrin-positive basal cells of the mouse epidermis. They are positive for sca-1 and negative for MHC class II and Flk1. They are not identical to the label-retaining population but are cycling cells in the mouse epidermis. Keratinocytes positive for sca-1 are located outside the stem cell containing bulge area of the mouse hair follicle. Forty-four human skin samples were analysed, and Esp cells were found at frequencies ranging from 0.01% to 5.39%, independently of age and body site. Human Esp cells did not express particular high levels of beta1 integrin. However, they expressed the half transporter ABCG2 and we identified high expression of this marker in the secretory duct epithelium of the sweat glands whereas low expression was found in the basal layer of the epidermis.