SEPARATION OF HUMAN EPIDERMAL STEM-CELLS FROM TRANSIT AMPLIFYING CELLS ON THE BASIS OF DIFFERENCES IN INTEGRIN FUNCTION AND EXPRESSION

The epidermis is believed to contain two types of proliferating cells: stem cells and cells with a lower capacity for self-renewal and highe r probability of undergoing terminal differentiation (transit amplifyi ng cells). We report that keratinocytes with characteristics of stem c ells can be isolated from cultured human epidermis on the basis of hig h surface expression of beta1 integrins and rapid adhesion to extracel lular matrix (ECM) proteins. Among keratinocytes there was a log linea r relationship between the relative level of beta1 integrins on the ce ll surface and proliferative capacity; furthermore, the cells with the highest colony-forming efficiency adhered most rapidly to type IV col lagen, fibronectin, or keratinocyte ECM. Proliferating keratinocytes t hat adhered more slowly had characteristics of transit amplifying cell s: after one to five rounds of division, all of their daughters underw ent terminal differentiation. Since stem cells can be isolated to grea ter 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.