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Science 342 (6163): 1226-1230

Copyright © 2013 by the American Association for the Advancement of Science

Interfollicular Epidermal Stem Cells Self-Renew via Autocrine Wnt Signaling

Xinhong Lim,1,* Si Hui Tan,2 Winston Lian Chye Koh,3 Rosanna Man Wah Chau,3 Kelley S. Yan,4 Calvin J. Kuo,4 Renée van Amerongen,1,{dagger} Allon Moshe Klein,5,{ddagger} Roel Nusse1,{ddagger}

Abstract: 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.

1 Department of Developmental Biology, Howard Hughes Medical Institute (HHMI), Institute for Stem Cell Biology and Regenerative Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
2 Program in Cancer Biology, School of Medicine, Stanford University, Stanford, CA, USA.
3 Department of Bio-engineering, Stanford University, Stanford, CA, USA.
4 Department of Medicine, School of Medicine, Stanford University, Stanford, CA, USA.
5 Department of Systems Biology, Harvard Medical School, Boston, MA, USA.

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

{dagger} Present address: Swammerdam Institute for Life Sciences, University of Amsterdam, Netherlands.

{ddagger} Corresponding author. E-mail: rnusse{at} (R.N.); allon_klein{at} (A.M.K.)

Permission to Proliferate.
J. Frede and P. H. Jones (2013)
Science 342, 1183-1184
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