The Epidermis Comprises Autonomous Compartments Maintained by Distinct Stem Cell Populations

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2013 Aug 20

PMID 23954751

Citations 166

Authors

Mahalia E Page

Patrick Lombard

Felicia Ng

Berthold Gottgens

Kim B Jensen

Affiliations

Soon will be listed here.

Abstract

The complex anatomy of the epidermis contains multiple adult stem cell populations, but the extent to which they functionally overlap during homeostasis, wound healing, and tumor initiation remains poorly defined. Here, we demonstrate that Lrig1(+ve) cells are highly proliferative epidermal stem cells. Long-term clonal analysis reveals that Lrig1(+ve) cells maintain the upper pilosebaceous unit, containing the infundibulum and sebaceous gland as independent compartments, but contribute to neither the hair follicle nor the interfollicular epidermis, which are maintained by distinct stem cell populations. In contrast, upon wounding, stem cell progeny from multiple compartments acquire lineage plasticity and make permanent contributions to regenerating tissue. We further show that oncogene activation in Lrig1(+ve) cells drives hyperplasia but requires auxiliary stimuli for tumor formation. In summary, our data demonstrate that epidermal stem cells are lineage restricted during homeostasis and suggest that compartmentalization may constitute a conserved mechanism underlying epithelial tissue maintenance.

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References

Choi N, Zhang B, Zhang L, Ittmann M, Xin L . Adult murine prostate basal and luminal cells are self-sustained lineages that can both serve as targets for prostate cancer initiation. Cancer Cell. 2012; 21(2):253-65. PMC: 3285423. DOI: 10.1016/j.ccr.2012.01.005. View

Barker N, van Oudenaarden A, Clevers H . Identifying the stem cell of the intestinal crypt: strategies and pitfalls. Cell Stem Cell. 2012; 11(4):452-60. DOI: 10.1016/j.stem.2012.09.009. View

Madisen L, Zwingman T, Sunkin S, Oh S, Zariwala H, Gu H . A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat Neurosci. 2009; 13(1):133-40. PMC: 2840225. DOI: 10.1038/nn.2467. View

Morris R, Liu Y, Marles L, Yang Z, Trempus C, Li S . Capturing and profiling adult hair follicle stem cells. Nat Biotechnol. 2004; 22(4):411-7. DOI: 10.1038/nbt950. View

Ousset M, Van Keymeulen A, Bouvencourt G, Sharma N, Achouri Y, Simons B . Multipotent and unipotent progenitors contribute to prostate postnatal development. Nat Cell Biol. 2012; 14(11):1131-8. DOI: 10.1038/ncb2600. View

Blanpain C . Stem cells: Skin regeneration and repair. Nature. 2010; 464(7289):686-7. DOI: 10.1038/464686a. View

Jensen K, Driskell R, Watt F . Assaying proliferation and differentiation capacity of stem cells using disaggregated adult mouse epidermis. Nat Protoc. 2010; 5(5):898-911. DOI: 10.1038/nprot.2010.39. View

Mootha V, Lindgren C, Eriksson K, Subramanian A, Sihag S, Lehar J . PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003; 34(3):267-73. DOI: 10.1038/ng1180. View

Clayton E, Doupe D, Klein A, Winton D, Simons B, Jones P . A single type of progenitor cell maintains normal epidermis. Nature. 2007; 446(7132):185-9. DOI: 10.1038/nature05574. View

10.

Petersson M, Brylka H, Kraus A, John S, Rappl G, Schettina P . TCF/Lef1 activity controls establishment of diverse stem and progenitor cell compartments in mouse epidermis. EMBO J. 2011; 30(15):3004-18. PMC: 3160179. DOI: 10.1038/emboj.2011.199. View

11.

Van Keymeulen A, Blanpain C . Tracing epithelial stem cells during development, homeostasis, and repair. J Cell Biol. 2012; 197(5):575-84. PMC: 3365500. DOI: 10.1083/jcb.201201041. View

12.

van der Weyden L, Alcolea M, Jones P, Rust A, Arends M, Adams D . Acute sensitivity of the oral mucosa to oncogenic K-ras. J Pathol. 2011; 224(1):22-32. PMC: 3627303. DOI: 10.1002/path.2853. View

13.

Langton A, Herrick S, Headon D . An extended epidermal response heals cutaneous wounds in the absence of a hair follicle stem cell contribution. J Invest Dermatol. 2007; 128(5):1311-8. DOI: 10.1038/sj.jid.5701178. View

14.

Levy V, Lindon C, Zheng Y, Harfe B, Morgan B . Epidermal stem cells arise from the hair follicle after wounding. FASEB J. 2007; 21(7):1358-66. DOI: 10.1096/fj.06-6926com. View

15.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

16.

Nagao K, Kobayashi T, Moro K, Ohyama M, Adachi T, Kitashima D . Stress-induced production of chemokines by hair follicles regulates the trafficking of dendritic cells in skin. Nat Immunol. 2012; 13(8):744-52. PMC: 4115277. DOI: 10.1038/ni.2353. View

17.

Jensen U, Yan X, Triel C, Woo S, Christensen R, Owens D . A distinct population of clonogenic and multipotent murine follicular keratinocytes residing in the upper isthmus. J Cell Sci. 2008; 121(Pt 5):609-17. PMC: 2963074. DOI: 10.1242/jcs.025502. View

18.

Alcolea M, Jones P . Tracking cells in their native habitat: lineage tracing in epithelial neoplasia. Nat Rev Cancer. 2013; 13(3):161-71. DOI: 10.1038/nrc3460. View

19.

Frances D, Niemann C . Stem cell dynamics in sebaceous gland morphogenesis in mouse skin. Dev Biol. 2012; 363(1):138-46. DOI: 10.1016/j.ydbio.2011.12.028. View

20.

Jaks V, Barker N, Kasper M, van Es J, Snippert H, Clevers H . Lgr5 marks cycling, yet long-lived, hair follicle stem cells. Nat Genet. 2008; 40(11):1291-9. DOI: 10.1038/ng.239. View