A single type of progenitor cell maintains normal epidermis

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Abstract
For more than 30 years, the accepted model of epithelial homeostasis has assumed that skin tissue is maintained by two separate populations of progenitor cells. Self-renewing stem cells were thought to give rise to short-lived progenitors that in turn form the new epidermis. Clayton et al. now suggest that this hypothesis can be replaced with a simpler model in which a single type of progenitor cell undergoes asymmetric division at a rate that ensures epidermal homeostasis. An alternative model for the homeostasis of adult epidermis posits posits only one type of stem cell undergoes both symmetric and asymmetric divisions to ensure epidermal homeostasis. A genetic approach of marking single cells in the adult mouse tail epidermis shows that the clones of labelled cells that arise from their inducible labelling approach are most likely to come from a single compartment of proliferating cells, which may undergo an unlimited number of divisions. According to the current model of adult epidermal homeostasis, skin tissue is maintained by two discrete populations of progenitor cells: self-renewing stem cells; and their progeny, known as transit amplifying cells, which differentiate after several rounds of cell division1,2,3. By making use of inducible genetic labelling, we have tracked the fate of a representative sample of progenitor cells in mouse tail epidermis at single-cell resolution in vivo at time intervals up to one year. Here we show that clone-size distributions are consistent with a new model of homeostasis involving only one type of progenitor cell. These cells are found to undergo both symmetric and asymmetric division at rates that ensure epidermal homeostasis. The results raise important questions about the potential role of stem cells on tissue maintenance in vivo.