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.
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We thank Y. Amagase for performing RT–PCR, E. Choolun and R. Walker for technical assistance, S. Penrhyn-Lowe and T. Mills for help with microscopy and R. Laskey, W. Harris, A. Philpott and C. Jones for comments. This work was funded by the Medical Research Council, Association for International Cancer Research and Cancer Research UK.
Author Contributions Experimental work was performed by E.C., D.P.D. and P.H.J., project planning by P.H.J. and D.J.W., biophysical analysis by B.D.S. and A.M.K.
Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.
This file contains Supplementary Methods, Supplementary Figures S1-S8 with Legends, Supplementary Table 1 and additional results. This section contains additional experimental methods, clone size data for back skin epidermis, the fate of differentiated clones, analysis of tissue growth, cell proliferation, cell migration, apoptosis and mitotic spindle orientation in tail epidermis. (PDF 1780 kb)
This file contains Supplementary Discussion and Supplementary Figures S9-S11 with Legends. This section contains a detailed analysis of why previous models do not explain the present data, and the derivation of the single compartment model of the epidermis. (PDF 253 kb)
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Clayton, E., Doupé, D., Klein, A. et al. A single type of progenitor cell maintains normal epidermis. Nature 446, 185–189 (2007). https://doi.org/10.1038/nature05574
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