Roles of MED1 in Quiescence of Hair Follicle Stem Cells and Maintenance of Normal Hair Cycling

MED1 (mediator complex subunit 1) is expressed by human epidermal keratinocytes and functions as a coactivator of several transcription factors. To elucidate the role of MED1 in keratinocytes, we established keratinocyte-specific Med1-null (Med1epi−/−) mice using the K5Cre/LoxP system. Development of the epidermis and appendages of Med1epi−/− mice were macroscopically and microscopically normal until the second catagen of the hair cycle. However, the hair cycle of Med1epi−/− mice was spontaneously repeated after the second telogen, which does not occur in wild-type (WT) mice. Hair follicles of Med1epi−/− mice could not enter anagen after 6 months of age, resulting in sparse pelage hair in older Med1epi−/− mice. Interfollicular epidermis (IFE) of Med1epi−/− mice was acanthotic and more proliferative than that of WT mice, whereas these findings were less evident in older Med1epi−/− mice. Flow cytometric analysis revealed that the numbers of hair follicle bulge stem cells were reduced in Med1epi−/− mice from a few months after birth. These results suggest that MED1 has roles in maintaining quiescence of keratinocytes and preventing depletion of the follicular stem cells.