Lgr6 Marks Stem Cells in the Hair Follicle that Generate all Cell Lineages of the Skin

Mammalian epidermis consists of three self-renewing compartments: the hair follicle, sebaceous gland and interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close relative to the Lgr5 stem cell gene. Lgr6 was expressed in the earliest embryonic hair placodes. In adult hair follicles, Lgr6+ cells resided in a previously uncharacterized region directly above the follicle bulge. They expressed none of the known bulge stem cell markers. Prenatal Lgr6+ cells established the hair follicle, sebaceous gland and interfollicular epidermis. Postnatally, Lgr6+ cells generated sebaceous gland and interfollicular epidermis, while contribution to hair lineages gradually diminished with age. Adult Lgr6+ cells executed long-term wound repair, including the formation of new hair follicles. We conclude that Lgr6 marks the most primitive epidermal stem cell. For the Lgr5 and Lgr6 stem cell comparison RNA was isolated from sorted GFPhi cell fractions of dorsal skin from Lgr5-EGFP-ires-CreERT2 mice and Lgr6-EGFP-ires-CreERT2, respectively (3 mice per group per sort).