title: The circadian clock in skin: implications for adult stem cells, tissue regeneration, cancer, aging, and immunity.
abstract: Historically, work on peripheral circadian clocks has been focused on organs and tissues that have prominent metabolic functions, such as the liver, fat, and muscle. In recent years, skin has emerged as a model for studying circadian clock regulation of cell proliferation, stem cell functions, tissue regeneration, aging, and carcinogenesis. Morphologically, skin is complex, containing multiple cell types and structures, and there is evidence for a functional circadian clock in most, if not all, of its cell types. Despite the complexity, skin stem cell populations are well defined, experimentally tractable, and exhibit prominent daily cell proliferation cycles. Hair follicle stem cells also participate in recurrent, long-lasting cycles of regeneration: the hair growth cycles. Among other advantages of skin is a broad repertoire of available genetic tools enabling the creation of cell type-specific circadian mutants. Also, due to the accessibility of skin, in vivo imaging techniques can be readily applied to study the circadian clock and its outputs in real time, even at the single-cell level. Skin provides the first line of defense against many environmental and stress factors that exhibit dramatic diurnal variations such as solar ultraviolet (UV) radiation and temperature. Studies have already linked the circadian clock to the control of UVB-induced DNA damage and skin cancers. Due to the important role that skin plays in the defense against microorganisms, it also represents a promising model system to further explore the role of the clock in the regulation of the body's immune functions. To that end, recent studies have already linked the circadian clock to psoriasis, one of the most common immune-mediated skin disorders. Skin also provides opportunities to interrogate the clock regulation of tissue metabolism in the context of stem cells and regeneration. Furthermore, many animal species feature prominent seasonal hair molt cycles, offering an attractive model for investigating the role of the clock in seasonal organismal behaviors.
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA Center for Complex Biological Systems, University of California, Irvine, Irvine, CA.
authors.forename: Maksim V
authors.initials: MV
authors.lastname: Plikus
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA Department of Biological Chemistry, University of California, Irvine, Irvine, CA Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, CA.
authors.forename: Elyse N
authors.initials: EN
authors.lastname: Van Spyk
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA.
authors.forename: Kim
authors.initials: K
authors.lastname: Pham
authors.affiliation: Kythera Biopharmaceuticals, Westlake Village, CA.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Geyfman
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Vivek
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Takahashi
authors.affiliation: Center for Complex Biological Systems, University of California, Irvine, Irvine, CA Department of Biological Chemistry, University of California, Irvine, Irvine, CA Division of Endocrinology, Department of Medicine, University of California, Irvine, Irvine, CA bogi@uci.edu.
authors.forename: Bogi
authors.initials: B
authors.lastname: Andersen
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D057906:Circadian Clocks / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics; D006801:Humans; D007109:Immunity / Q000235:genetics; D009154:Mutation; D011565:Psoriasis / Q000209:etiology / Q000276:immunology; D012038:Regeneration; D012867:Skin / Q000166:cytology; D015595:Skin Aging / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000503:physiopathology*; D012879:Skin Physiological Phenomena; D013696:Temperature; D014466:Ultraviolet Rays / Q000009:adverse effects
keywords: UV exposure; aging; autoimmune diseases; cancer; cell cycle; hair follicle; immunity; regeneration; skin; stem cells