Hair Follicle Stem Cell differentiation is inhibited through the

LEIROS GUSTAVO; ATTORRESI ALEJANDRA; BALAÑÁ , MARÍA EUGENIA

Paris

Conferencia; 'Advances in Stem Cell Research: Development, Regeneration and Disease'; 2011

EMBO (European Molecular Biology Organization ) - Institut Pasteur

The hair follicle (HF) contains a pool of multipotent epithelial stem cells in the bulge area, that give rise to a wide range of differentiated cell types in skin. The HF is a regenerating system, which physiologically undergoes numerous cycles of growth, regression and rest during adult life. Its formation begins when signals from the mesenchyme-derived dermal papilla cells (DPC) reach multipotent epidermal stem cells in the bulge region. In androgenetic alopecia (AGA) androgen action causes HF miniaturization and baldness through a mechanism which remains unclear. Circulating androgens act on DPC and alter regulatory paracrine factors probably involved in the differentiation and proliferation of the HF multipotent cells. The aim of this work is to determine the role of androgens in the differentiation of scalp HF stem cells. In a co-culture model with human DPC from patients suffering AGA and HF stem cells, androgens treatment abrogates hair differentiation. The expression of the keratin K6hf, a hair differentiation marker, was significantly downregulated in HF stem cells co-cultured with androgen-treated DPC. Wnt/©¬-catenin signaling is known to positively affect mammalian hair growth. Analysis of the cytoplasmic pool of ¥â-catenin by  Western blot showed that the ratio cytoplasmatic/total ¥â-catenin  is significantly lower in androgen-treated DPC showing  that androgens are able to inhibit canonical Wnt signalling. LiCl, which mimics the effects of Wnt signalling activation, restored the differentiation ability of androgen- treated DPC. Glycogen synthase kinase-3¥â  (GSK-3¥â) inhibits Wnt signaling by phosphorylating ¥â-catenin. Finally, in the presence of androgens, we found an upregulation of GSK-3¥â inhibitory activity on this pathway. These results suggest that androgens may modulate the secretion of paracrine factors involved in normal scalp HF stem cell differentiation inactivating the canonical Wnt signaling pathway.