Integrin-linked kinase regulates the niche of quiescent epidermal stem cells

Nat Commun. 2015 Sep 8:6:8198. doi: 10.1038/ncomms9198.

Abstract

Stem cells reside in specialized niches that are critical for their function. Quiescent hair follicle stem cells (HFSCs) are confined within the bulge niche, but how the molecular composition of the niche regulates stem cell behaviour is poorly understood. Here we show that integrin-linked kinase (ILK) is a key regulator of the bulge extracellular matrix microenvironment, thereby governing the activation and maintenance of HFSCs. ILK mediates deposition of inverse laminin (LN)-332 and LN-511 gradients within the basement membrane (BM) wrapping the hair follicles. The precise BM composition tunes activities of Wnt and transforming growth factor-β pathways and subsequently regulates HFSC activation. Notably, reconstituting an optimal LN microenvironment restores the altered signalling in ILK-deficient cells. Aberrant stem cell activation in ILK-deficient epidermis leads to increased replicative stress, predisposing the tissue to carcinogenesis. Overall, our findings uncover a critical role for the BM niche in regulating stem cell activation and thereby skin homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basement Membrane
  • Blotting, Western
  • Carcinogens / pharmacology
  • Cell Adhesion
  • Cell Adhesion Molecules / metabolism
  • Cell Proliferation
  • Electrophoresis, Polyacrylamide Gel
  • Epidermal Cells
  • Extracellular Matrix / genetics*
  • Extracellular Matrix / metabolism
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Gene Knockout Techniques
  • Hair Follicle / cytology*
  • Immunohistochemistry
  • Kalinin
  • Keratinocytes / metabolism*
  • Laminin / metabolism
  • Mice
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Skin / drug effects
  • Stem Cell Niche / genetics*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transforming Growth Factor beta
  • Wnt Signaling Pathway

Substances

  • Carcinogens
  • Cell Adhesion Molecules
  • Laminin
  • Transforming Growth Factor beta
  • laminin 10
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases
  • Tetradecanoylphorbol Acetate

Associated data

  • GEO/GSE68846