Hair follicle cells

Epithelial tissues contain a-5 and a-3 laminin isoforms

Epithelial tissues are sheets of cells that line the surfaces and cavities of the whole body, including the skin, oral cavity, lung, gastrointestinal and urinary tracts, hair follicles, and many glands. The epithelial cells are polarized with the basolateral surface resting on a basement membrane (BM) that contains high levels of alpha-5 laminins and laminin-332. Epithelial BM also contains laminin-311 and to a lesser extent laminin-321 (Domogatskaya, 2012). Laminin-311 forms a covalent complex with laminin-332 in epithelial tissue (Champliaud, 1996) and has been shown to participate in mechanically induced signal transduction after mechanical stimulation (Jones, 2005).

Laminin-332 and laminin-511 constitute the hair follicle stem cell niche

Laminin-332 and laminin-511 are the major constituents of the BM of the hair follicle (Morgner, 2015). The laminin-332 expression is higher in the interfollicular epidermis (IFE) compared with the deeper portions of the hair follicle. Laminin-511 is less abundant beneath the IFE but has the strongest expression at the isthmus region and around the hair germ (Morgner, 2015), which is essential for hair follicle down-growth (Gao, 2008). Dermal papilla from laminin-511 mutants show developmental defects (Gao, 2008). Laminin-511 is the primary laminin of the early developing hair. The absence of laminin-511 in transgenic mice leads to several developmental abnormalities, including the arrest of hair development and deficient Shh expression in hair follicles (Li, 2003). Skin grafts from Lama5-null mouse embryos grafted onto healthy mice fail to grow hair whereas purified laminin-511 restores hair development in the Lama5-null skin (Li, 2003). In humans and mice, the absence of laminin-332 results in extensive skin blistering and lethality a few days after birth, highlighting its importance for epidermal architecture (Morgner, 2015).

The ratio between laminin-332 and -511 regulates hair follicle bulge stem cell activation

The hair growth cycle involves three stages: the growth phase (anagen), the regression phase (catagen), and the quiescent phase (telogen). During each anagen phase, follicles divide rapidly, adding to the hair shaft. During the catagen and telogen phase, follicles reset and prepare their stem cells to receive a signal to start the next growth phase. Hair loss occurs when the balance between those stages changes. Laminin-511 is upregulated in the anagen phase and exogenous laminin-521 and laminin-511 make adult human hair follicles grow faster (Sugawara, 2007). Laminin-511 is downregulated during the anagen-to-catagen transition, and this downregulation is required for catagen progression. In contrast, laminin-332 is upregulated in the catagen and antagonizes hair growth induced by laminin-511 (Sugawara, 2007). The integrin receptor subunit β1 is central for the maintenance of the quiescent bulge stem cell pool (Morgner, 2015). Inhibition of the β1 integrin disrupted dermal papilla primary cilia formation and hair development (DeRouen, 2010).

Laminin-511 promotes Tgf-β signaling which makes hair follicle stem cells (HFSC) more receptive to activating signals. Contrary, laminin-332 suppresses Wnt/β-catenin signaling that is required for HFSC differentiation. The ratio between the two laminin isoforms regulates key signaling pathways that determine somatic stem cell activation within the bulge niche (Morgner, 2015).

Biolaminin 511 in HFSC culture

Exogenous full-length laminin-511 enhances the growth of hair follicle stem cells, whereas the addition of laminin-332 antagonizes this effect. FACS-purified hair follicle stem cells attach optimally to laminin-511 coated plates with about 6 times higher well area coverage compared to other cell culture matrices, such as collagen I, fibronectin, or Matrigel (Lay, 2016).