Interfollicular epidermal stem cells self-renew via autocrine Wnt signaling

Science. 2013 Dec 6;342(6163):1226-30. doi: 10.1126/science.1239730.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Autocrine Communication*
  • Axin Protein / genetics
  • Axin Protein / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Cells, Cultured
  • Epidermal Cells*
  • Epidermis / injuries
  • Epidermis / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / metabolism
  • Gene Expression
  • Homeostasis
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Mice
  • Regeneration
  • Skin / injuries
  • Stem Cell Niche
  • Stem Cells / cytology
  • Stem Cells / physiology*
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway*
  • Wound Healing
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Axin Protein
  • Axin2 protein, mouse
  • Dkk1 protein, mouse
  • Dkk3 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Wnt Proteins
  • beta Catenin