title: 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.
authors.affiliation: Department of Regenerative Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. nakajima@r-derma.med.osaka-u.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakajima
authors.forename: Shigeki
authors.initials: S
authors.lastname: Inui
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fushimi
authors.forename: Fumihito
authors.initials: F
authors.lastname: Noguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Janardan K
authors.initials: JK
authors.lastname: Reddy
authors.forename: Satoshi
authors.initials: S
authors.lastname: Itami
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D000078404:Epidermal Cells; D004817:Epidermis / Q000254:growth & development; D005260:Female; D006197:Hair / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D019426:Integrases / Q000235:genetics; D053555:Keratin-5 / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology; D008297:Male; D056913:Mediator Complex Subunit 1 / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055758:SOX9 Transcription Factor / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
chemical_list: C503940:KRT5 protein, human; D053555:Keratin-5; C538856:Med1 protein, mouse; D056913:Mediator Complex Subunit 1; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; C045073:Cre recombinase; D019426:Integrases