Adhesive properties of human basal epidermal cells: An analysis of keratinocyte stem cells, transit amplifying cells, and postmitotic differentiating cells

The basal layer of human epidermis is a heterogeneous population of proliferative and differentiating cells that can be divided into at least three functionally discrete compartments: keratinocyte stem cells, transit amplifying cells, and postmitotic differentiating cells. Basal cells adhere to the underlying basement membrane via integrins, and although decreased adhesion is a key event in epidermal differentiation, the specific role of particular integrins is poorly understood. We report here on the comparative expression and function of the beta(1) versus alpha(6)beta(4) integrins in keratinocyte stem cells, transit amplifying cells, and postmitotic differentiating cells of neonatal human foreskin epidermis. Adhesion assays demonstrate that both keratinocyte stem cells and transit amplifying cells comprise rapidly adhering cells that exhibit high levels of functional beta(1) and alpha(6)beta(4) integrins. Interestingly, a proportion of basal cells that have begun to differentiate in vivo within the basal layer as determined by their expression of the differentiation-specific markers K10 and involucrin also retain high levels of activated beta(1) integrin, but downregulate alpha(6)beta(4) expression selectively (termed alpha(6)(dim)beta(1)(bri)). These cells also retain their adhesive capacity, indicating that induction of differentiation in vivo does not correlate with decreased beta(1) integrin expression or function. We have previously reported on the use of alpha(6) integrin in conjunction with a proliferation associated marker (10G7 ag) to separate keratinocyte stem cells (phenotype alpha(6)(bri)10G7(dim)) from other basal cells (Li et al. Proc Natl Acad Sci 95:3902-3907 1998). A comparison of the long-term proliferative potential of beta(1)(bri)10G7(dim) cells with alpha(6)(bri)10G7(dim) showed that selection of alpha(6)(bri)10G7(dim) allows the isolation of a purer fraction of keratinocyte stem cells.