| Hair follicle is one of the basic structures in skin, hair is maintained through a cyclic process that includes periodic regeneration of hair follicles in a stem-celldependent manner. Hair follicle stem cells are important adult stem cells, and they are fine models to study the proliferation and differentiation of adult stem cells due to their period changes.Except for their high proliferative capacity , another attractive poverty of hair follicle stem cells is they multipotent, they are able to give rise not only to hair follicle but also epidermis and sebaceous gland. However, hair follicle stem cells prefer hair destiny in vivo, unless the injury of epidimal or sytogland occurs. In 1990, Cosarelis et al. proposed "The Bulge activated hypothesis", they think the signal moleculars emit from the dermal papillar induce the downward migration and differentiation of hair follicle stem cells. Recently, this view has been supported by lots of research evidences and is widely accepted by many researchers.There are many signal moleculars involved in the interaction of dermal papilla cells and hair follicle stem cell, and Wnt/Lef-1 signaling passway is of importance in this process. Many research findings revealed when Lef-1 is knocked out, there is a completely loss in vibrissa follicle and a significant reduction in hair follicle;by contrast, the transgene mouse expressing stabilised Lef-1 have a mass of nevo hair follicle in epidermis and devolop skin tumors consequencely. Therefore, Lef-1 palys an fundamental role in morphogenesis and cylce of the hair follicle.Then, whether Lef-1 has an effect on the differentiation of hair follicle Bulge stem cells in vitro and how it exert its function in this process is still unclear. At present, the understanding on these questions remain superficial yet.In our study, we explored the expression pattern of Lef-1 in the hair cycle adopting immuochemistry and RT-PCR methods; simulated the differentiation of hair follicle Bulge stem cells in vivo utilized Transwell system and dermal papilla induced mediate respectively;moreover, Lef-1 gene and N-terminal truncated Lef-1 gene overexpression in primary hair follicle Bulge stem cells have been manipulated in vitro by gene transfection and observed its influence on cell deffirentiation of hair follicle stem cells.The main results are as follows:①The expression of Lef-1 in narmao hair cycle is dynamic. In Anagen, Lef-1 is expressed in the nuclear of bulb and ORS of the hair follicle,as its futher growth,this nuclear expression pattern gradually converts into cytoplasm expression; In Catagen ,the staining of Lef-1 weaks obviously,and it disappears in ORS; In Telogen, the expression of Lef-1 appears in the lateral of bulge again and is apparent in IRS.②After the induction by Transwell system and dermal papilla induced mediate, we found that the expression of specific marker of hair diffirentiation- keratin 6 was obviously enhanced, and the effect of Transwell system was slightly better than dermal papilla induced mediate.③In the progress of hair follicle Bulge stem cells in vitro differentiataion, we found that the expression of Lef-1 and its corelated factorsβ-catenin,c-Myc was consistent, which were all significantedly enhanced. Futhermore, the translocation of Lef-1 was ealier thanβ-catenin.④Transint transfection of Lef-1 gene induced the translocation ofβ-catenin, and activated hair follicle Bulge stem cells to choose the fate of hair; In contrast, N-terminal truncated Lef-1 gene had little effect on the translocation ofβ-catenin and the fate of hair differentiataion in hair follicle Bulge cells.In conclusion, our results implicate that Lef-1 plays an important role in differentiation of hair follicle Bulge stem cells: it promoted the translocation ofβ-catenin, activated the downstream genes, and utilimately induced the differentiation of Bulge stem cells into hair direction.
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