title: Resting no more: re-defining telogen, the maintenance stage of the hair growth cycle.
abstract: The hair follicle (HF) represents a prototypic ectodermal-mesodermal interaction system in which central questions of modern biology can be studied. A unique feature of these stem-cell-rich mini-organs is that they undergo life-long, cyclic transformations between stages of active regeneration (anagen), apoptotic involution (catagen), and relative proliferative quiescence (telogen). Due to the low proliferation rate and small size of the HF during telogen, this stage was conventionally thought of as a stage of dormancy. However, multiple lines of newly emerging evidence show that HFs during telogen are anything but dormant. Here, we emphasize that telogen is a highly energy-efficient default state of the mammalian coat, whose function centres around maintenance of the hair fibre and prompt responses to its loss. While actively retaining hair fibres with minimal energy expenditure, telogen HFs can launch a new regeneration cycle in response to a variety of stimuli originating in their autonomous micro-environment (including its stem cell niche) as well as in their external tissue macro-environment. Regenerative responses of telogen HFs change as a function of time and can be divided into two sub-stages: early 'refractory' and late 'competent' telogen. These changing activities are reflected in hundreds of dynamically regulated genes in telogen skin, possibly aimed at establishing a fast response-signalling environment to trauma and other disturbances of skin homeostasis. Furthermore, telogen is an interpreter of circadian output in the timing of anagen initiation and the key stage during which the subsequent organ regeneration (anagen) is actively prepared by suppressing molecular brakes on hair growth while activating pro-regenerative signals. Thus, telogen may serve as an excellent model system for dissecting signalling and cellular interactions that precede the active 'regenerative mode' of tissue remodeling. This revised understanding of telogen biology also points to intriguing new therapeutic avenues in the management of common human hair growth disorders.
authors.affiliation: Department of Biological Chemistry, University of California Irvine, Irvine, CA 92697, U.S.A.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Geyfman
authors.affiliation: Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, Center for Complex Biological Systems, University of California Irvine, Irvine, CA 92697, U.S.A.
authors.forename: Maksim V
authors.initials: MV
authors.lastname: Plikus
authors.affiliation: Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, U.S.A.
authors.forename: Elsa
authors.initials: E
authors.lastname: Treffeisen
authors.affiliation: Department of Biological Chemistry, University of California Irvine, Irvine, CA 92697, U.S.A.|Department of Medicine, University of California Irvine, Irvine, CA 92697, U.S.A.|Institute for Genomics and Bioinformatics, University of California Irvine, Irvine, CA 92697, U.S.A.
authors.forename: Bogi
authors.initials: B
authors.lastname: Andersen
authors.affiliation: Dermatology Research Centre, Institute of Inflammation and Repair, University of Manchester, Manchester, M13 9PL, U.K.|Department of Dermatology, University of Munster, K-48149, Munster, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000818:Animals; D006197:Hair / Q000254:growth & development*; D018859:Hair Follicle / Q000502:physiology*
keywords: energy; gene expression; hair growth cycle; hair regeneration; telogen