Separation of human epidermal stem cells from transit amplifying cells on the basis of differences in integrin function and expression

Abstract

The epidermis is believed to contain two types of proliferating cells: stem cells and cells with a lower capacity for self-renewal and higher probability of undergoing terminal differentiation (transit amplifying cells). We report that keratinocytes with characteristics of stem cells can be isolated from cultured human epidermis on the basis of high surface expression of beta 1 integrins and rapid adhesion to extracellular matrix (ECM) proteins. Among keratinocytes there was a log linear relationship between the relative level of beta 1 integrins on the cell surface and proliferative capacity; furthermore, the cells with the highest colony-forming efficiency adhered most rapidly to type IV collagen, fibronectin, or keratinocyte ECM. Proliferating keratinocytes that adhered more slowly had characteristics of transit amplifying cells: after one to five rounds of division, all of their daughters underwent terminal differentiation. Since stem cells can be isolated to greater than 90% purity on the basis of their adhesive properties, it will now be possible to investigate the mechanisms that regulate the fate of their progeny.