Permission to Proliferate

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Science  06 Dec 2013:
Vol. 342, Issue 6163, pp. 1183-1184
DOI: 10.1126/science.1248274

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Maintaining proliferating adult tissues involves a critical balance. Exactly the right number of cells must be produced to replace those lost from the tissue; otherwise, tissue failure or tumor formation will ensue. In mammalian epidermis, differentiated cells are shed from the tissue surface and replaced by dividing stem cells in the basal layer (see the figure) (1). On average, each cell division generates one daughter that goes on to divide and produce more such cells, while the other cell differentiates and migrates to the surface of the epidermis (2). Cell production must be adjusted in response to surface abrasion or injury, implying that proliferation is regulated by signals from nearby cells. One candidate for this role is the secreted protein Wnt, as mutations that disrupt its downstream cellular signaling pathway result in hairless, thin epidermis (3, 4). Two studies—by Lim et al. (5) on page 1226 of this issue and by Choi et al. (6)—elucidate how Wnt functions in the epidermis. They show that Wnt and Wnt inhibitors balance the renewal and differentiation of epidermal stem cells and are both secreted by the stem cells themselves. This suggests autocrine regulation as distinct from the prevailing idea that stem cells are regulated by signals from other cell types in a “niche.”