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

In the present study the authors conclude that the precise ratio between LN-332 and LN-511 adjusts activities of key signalling pathways that determine SC activation within the hair follicle bulge niche. They suggest that integrin-linked kinase (ILK) is required for the maintenance of quiescent bulge SCs through remodelling of the ECM niche, thereby governing the activation and maintenance of hair follicle stem cells (HFSCs). ILK mediates deposition of inverse laminin-332 and -511 gradients within the basement membrane (BM) wrapping the hair follicles. The precise ratio of LN-511 and LN-332 regulates core SC fate-determining signalling pathways and that this ratio is disturbed in the absence of ILK, leading to aberrant SC activation and failure to re-establish quiescence. The BM composition tunes activities of Wnt and transforming growth factor-β pathways and subsequently regulates HFSC activation. LN-511, present at low levels around the bulge and at higher levels around the hair germ/TACs, promotes Tgf-β signalling, whereas LN-332, highly expressed along the IFE and to a lesser extent along the upper regions of HFs, suppresses Wnt/β-catenin signalling. Notably, reconstituting an optimal laminin microenvironment restores the altered signalling in ILK-deficient cells.