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

Abstract

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 (Med1(epi-/-)) mice using the K5Cre/LoxP system. Development of the epidermis and appendages of Med1(epi-/-) mice were macroscopically and microscopically normal until the second catagen of the hair cycle. However, the hair cycle of Med1(epi-/-) mice was spontaneously repeated after the second telogen, which does not occur in wild-type (WT) mice. Hair follicles of Med1(epi-/-) mice could not enter anagen after 6 months of age, resulting in sparse pelage hair in older Med1(epi-/-) mice. Interfollicular epidermis (IFE) of Med1(epi-/-) mice was acanthotic and more proliferative than that of WT mice, whereas these findings were less evident in older Med1(epi-/-) mice. Flow cytometric analysis revealed that the numbers of hair follicle bulge stem cells were reduced in Med1(epi-/-) 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.