title: Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling.
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.
authors: 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.
authors: Xinhong
authors: X
authors: Lim
authors: Si Hui
authors: SH
authors: Tan
authors: Winston Lian Chye
authors: WL
authors: Koh
authors: Rosanna Man Wah
authors: RM
authors: Chau
authors: Kelley S
authors: KS
authors: Yan
authors: Calvin J
authors: CJ
authors: Kuo
authors: Renée
authors: R
authors: van Amerongen
authors: Allon Moshe
authors: AM
authors: Klein
authors: Roel
authors: R
authors: Nusse
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019898:Autocrine Communication; D060466:Axin Protein / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000293:injuries / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D012038:Regeneration; D012867:Skin / Q000293:injuries; D055153:Stem Cell Niche; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D014945:Wound Healing; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; C111729:Axin2 protein, mouse; C501127:Dkk1 protein, mouse; C405061:Dkk3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D051153:Wnt Proteins; D051176:beta Catenin