Lgr6 Marks Stem Cells in the Hair Follicle That Generate All Cell Lineages of the Skin
- Hugo J. Snippert1,*,
- Andrea Haegebarth1,*,
- Maria Kasper2,
- Viljar Jaks2,
- Johan H. van Es1,
- Nick Barker1,
- Marc van de Wetering1,
- Maaike van den Born1,
- Harry Begthel1,
- Robert G. Vries1,
- Daniel E. Stange1,
- Rune Toftgård2 and
- Hans Clevers1,†
- 1Hubrecht Institute–KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht, Uppsalalaan 8, 3584 CT Utrecht, Netherlands.
- 2Karolinska Institutet, Center for Biosciences and Department of Biosciences and Nutrition, Novum, SE-141 57 Huddinge, Sweden.
- †To whom correspondence should be addressed. E-mail: h.clevers{at}hubrecht.eu
Abstract
Mammalian epidermis consists of three self-renewing compartments: the hair follicle, the sebaceous gland, and the interfollicular epidermis. We generated knock-in alleles of murine Lgr6, a close relative of 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, whereas 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.
- Received for publication 16 November 2009.
- Accepted for publication 10 February 2010.
