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 β1versus α6β4 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 β1 and α6β4 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 β1 integrin, but downregulate α6β4 expression selectively (termed α6dimß1bri). These cells also retain their adhesive capacity, indicating that induction of differentiation in vivo does not correlate with decreased β1 integrin expression or function. We have previously reported on the use of α6 integrin in conjunction with a proliferation associated marker (10G7 ag) to separate keratinocyte stem cells (phenotype α6bri10G7dim) from other basal cells (Li et al.Proc Natl Acad Sci 95:3902–3907 1998). A comparison of the long-term proliferative potential of ß1bri10G7dim cells withα6bri10G7dim showed that selection of α6bri10G7dim allows the isolation of a purer fraction of keratinocyte stem cells