Integrin-linked kinase regulates the niche of quiescent epidermal stem cells.
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.
Paul Gerson Unna Group 'Skin Homeostasis and Ageing', Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
Jessica
J
Morgner
Paul Gerson Unna Group 'Skin Homeostasis and Ageing', Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
Sushmita
S
Ghatak
Computational RNA Biology and Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
Tobias
T
Jakobi
Computational RNA Biology and Ageing, Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.
Christoph
C
Dieterich
Center for Biochemistry, Medical Faculty, University of Cologne, Cologne 50931, Germany.
Monique
M
Aumailley
Paul Gerson Unna Group 'Skin Homeostasis and Ageing', Max Planck Institute for Biology of Ageing, Cologne 50931, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne 50931, Germany.
Sara A
SA
Wickström
D000818:Animals; D001485:Basement Membrane; D015153:Blotting, Western; D002273:Carcinogens / Q000494:pharmacology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D004591:Electrophoresis, Polyacrylamide Gel; D000078404:Epidermal Cells; D005109:Extracellular Matrix / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D055786:Gene Knockout Techniques; D018859:Hair Follicle / Q000166:cytology*; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D012867:Skin / Q000187:drug effects; D055153:Stem Cell Niche / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016212:Transforming Growth Factor beta; D060449:Wnt Signaling Pathway; D000097794:Kalinin; D000099200:Scaffold Protein ILK
D002273:Carcinogens; D015815:Cell Adhesion Molecules; D007797:Laminin; D017346:Protein Serine-Threonine Kinases; D013755:Tetradecanoylphorbol Acetate; D016212:Transforming Growth Factor beta; D000097794:Kalinin; D000099200:Scaffold Protein ILK; C119013:laminin 10