The Stem Cell Quiescence and Niche Signaling is Disturbed in the Hair Follicle of the Hairpoor Mouse, an MUHH Model Mouse.

Abstract Background Hair follicle stem cells (HFSC) play an essential role in the maintenance of hair homeostasis during the hair cycle in which HFSC remain quiescent most of its duration. The hairpoor mouse (+/HrHp), an animal model of Marie-Unna Hypotrichosis (MUHH), exhibits over-expression of Hairless in the bulge, inner root sheath and outer root sheath of HF and exhibits the same phenotype as in MUHH patients manifesting sparse hair with progression to alopecia with age. In this study, we aimed to understand the hair cycle and the status of HFSC during the hair cycle of the hairpoor mouse to delineate the pathogenesis of MUHH. Methods To define the state of the hair follicle, H&E staining was performed. FACS analysis and immunostaining was utilized at the 1st and 2nd telogen stages to observe the HFSCs. Label retaining assay was carried out to determine the quiescent state of hair follicle. Expression of factors in involved in the niche signaling and the Wnt signaling was determined using qRT-PCR. Results We found that the number of hair follicle was drastically decreased after 1st telogen, then followed by the intensified disturbance in the hair cycle with shorter anagen as well as 2nd telogen in the hairpoor mouse. The number of CD34 expressing bulges as well as cells were dramatically reduced at the telogen of the HFs and the high proliferation of bulge cells was prominent, suggesting the loss of HFSC quiescence in the hairpoor mouse. The increased cell proliferation in HF was reiterated following the synchronization of hair cycle, leading to accelerating HF cycling. The expression of Fgf18 and Bmp6, the factors involved in the HFSC quiescence, was reduced in the HFSC niche of the hairpoor mouse. Furthermore, expression of Wnt signaling molecules including Wnt7b, Wnt10b and Sfrp1 were disturbed inducing the telogen to anagen transition of HFs in the hairpoor mouse. Conclusions These results indicate that the quiescent state of HFSC is not properly maintained in the hairpoor mouse and consequently leading HFs to the completely disarrayed hair cycle. These findings may provide an understanding of an underlying mechanism by which alopecia develops with age in MUHH patients.