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Distinct contribution of stem and progenitor cells to epidermal maintenance

Abstract

The skin interfollicular epidermis (IFE) is the first barrier against the external environment and its maintenance is critical for survival. Two seemingly opposite theories have been proposed to explain IFE homeostasis. One posits that IFE is maintained by long-lived slow-cycling stem cells that give rise to transit-amplifying cell progeny, whereas the other suggests that homeostasis is achieved by a single committed progenitor population that balances stochastic fate. Here we probe the cellular heterogeneity within the IFE using two different inducible Cre recombinase–oestrogen receptor constructs targeting IFE progenitors in mice. Quantitative analysis of clonal fate data and proliferation dynamics demonstrate the existence of two distinct proliferative cell compartments arranged in a hierarchy involving slow-cycling stem cells and committed progenitor cells. After wounding, only stem cells contribute substantially to the repair and long-term regeneration of the tissue, whereas committed progenitor cells make a limited contribution.

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Figure 1: K14-Cre-ER and Inv-Cre-ER target IFE progenitors with different survival characteristics.
Figure 2: Inv-Cre-ER targets IFE CP cells.
Figure 3: K14-Cre-ER targets IFE SCs.
Figure 4: Molecular signature of K14 SC and Inv CP cells.
Figure 5: Massive and sustained contribution of K14 SC during wound healing.

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Gene Expression Omnibus

Data deposits

The data discussed in this publication have been deposited in the NCBI Gene Expression Omnibus and are accessible through GEO Series accession number GSE36688.

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Acknowledgements

We thank F. Bollet-Quivogne and J.-M. Vanderwinden for their help with confocal imaging. C.B. and P.A.S. are chercheur qualifié, G.M. and S.B. are supported by fellowship of the FRS/FNRS. B.D. is supported by TELEVIE. C.B. is an investigator of WELBIO. This work was supported by the FNRS, the program d’excellence CIBLES of the Wallonia Region, a research grant from the Fondation Contre le Cancer, the ULB fondation, the fond Gaston Ithier, the European Research Council (ERC) and the EMBO Young Investigator Program.

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C.B., G.M., B.D., S.D., P.A.S. and B.D.S. designed the experiments and performed data analysis. G.M., S.D., B.D. and K.K.Y. performed all the experiments. S.B. performed bioinformatic analysis of the microarray. C.B. and B.D.S. wrote the manuscript.

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Correspondence to Benjamin D. Simons or Cédric Blanpain.

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Mascré, G., Dekoninck, S., Drogat, B. et al. Distinct contribution of stem and progenitor cells to epidermal maintenance. Nature 489, 257–262 (2012). https://doi.org/10.1038/nature11393

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