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

• Published in: Nature communications Vol. 6; no. 1; p. 8198
• Main Authors: Morgner, Jessica, Ghatak, Sushmita, Jakobi, Tobias, Dieterich, Christoph, Aumailley, Monique, Wickström, Sara A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.09.2015; Nature Publishing Group; Nature Pub. Group
• Subjects: 13/100; 13/106; 13/31; 13/51; 14/19; 38/77; 38/89; 38/91; 631/136/532/2443; 631/45/607/275; 631/80/86; 64/60; Animals; Basement Membrane; Blotting, Western; Carcinogenesis; Carcinogens; Carcinogens - pharmacology; Cell activation; Cell Adhesion; Cell Adhesion Molecules - metabolism; Cell Proliferation; Chemical composition; Electrophoresis, Polyacrylamide Gel; Epidermal Cells; Epidermis; Extracellular matrix; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Flow Cytometry; Fluorescent Antibody Technique; Follicles; Gene Knockout Techniques; Growth factors; Hair; Hair Follicle - cytology; Homeostasis; Humanities and Social Sciences; ILK protein; Immunohistochemistry; Kalinin; Keratinocytes - metabolism; Kinases; Laminin; Laminin - metabolism; Mice; multidisciplinary; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Real-Time Polymerase Chain Reaction; Science; Science (multidisciplinary); Sequence Analysis, RNA; Signal transduction; Skin; Skin - drug effects; Stem Cell Niche - genetics; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Transforming growth factor; Transforming Growth Factor beta; Transforming growth factor-b; Wnt protein; Wnt Signaling Pathway
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms9198

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. Integrin-linked kinase (ILK) is known to modulate the extracellular matrix and hair follicle morphogenesis. Here, Morgner et al. show that lack of ILK causes an aberrant ratio of basement membrane laminins, activating stem cells and predisposing skin to carcinogenesis.