Interfollicular Epidermal Stem Cells Self-Renew via Autocrine Wnt Signaling

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Science  06 Dec 2013:
Vol. 342, Issue 6163, pp. 1226-1230
DOI: 10.1126/science.1239730

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Epithelial Stem Cells

Much remains to be known about how epithelial stem cells are generated and maintained. Lim et al. (p. 1226; see the Perspective by Frede and Jones) describe a mechanism of stem cell maintenance where epidermal stem cells generate their own self-renewing Wnt signals rather than being controlled by adjacent “niche” signals. These stem cells also express secreted Wnt inhibitors that become localized to more differentiated progeny cells. These autocrine Wnt signals and paracrine long-range Wnt inhibitors may balance stem cell self-renewal and differentiation.


The skin is a classical example of a tissue maintained by stem cells. However, the identity of the stem cells that maintain the interfollicular epidermis and the source of the signals that control their activity remain unclear. Using mouse lineage tracing and quantitative clonal analyses, we showed that the Wnt target gene Axin2 marks interfollicular epidermal stem cells. These Axin2-expressing cells constitute the majority of the basal epidermal layer, compete neutrally, and require Wnt/β-catenin signaling to proliferate. The same cells contribute robustly to wound healing, with no requirement for a quiescent stem cell subpopulation. By means of double-labeling RNA in situ hybridization in mice, we showed that the Axin2-expressing cells themselves produce Wnt signals as well as long-range secreted Wnt inhibitors, suggesting an autocrine mechanism of stem cell self-renewal.

  • * Present address: Institute ofMedical Biology, A*STAR, Singapore.

  • Present address: Swammerdam Institute for Life Sciences, University of Amsterdam, Netherlands.

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