title: Brg1 governs a positive feedback circuit in the hair follicle for tissue regeneration and repair.
abstract: Hair follicle stem cells (bulge cells) are essential for hair regeneration and early epidermal repair after wounding. Here we show that Brg1, a key enzyme in the chromatin-remodeling machinery, is dynamically expressed in bulge cells to control tissue regeneration and repair. In mice, sonic hedgehog (Shh) signals Gli to activate Brg1 in bulge cells to begin hair regeneration, whereas Brg1 recruits NF-κB to activate Shh in matrix cells to sustain hair growth. Such reciprocal Brg1-Shh interaction is essential for hair regeneration. Moreover, Brg1 is indispensable for maintaining the bulge cell reservoir. Without Brg1, bulge cells are depleted over time, partly through the ectopic expression of the cell-cycle inhibitor p27(Kip1). Also, bulge Brg1 is activated by skin injury to facilitate early epidermal repair. Our studies demonstrate a molecular circuit that integrates chromatin remodeling (Brg1), transcriptional regulation (NF-κB, Gli), and intercellular signaling (Shh) to control bulge stem cells during tissue regeneration.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Yiqin
authors.initials: Y
authors.lastname: Xiong
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Ching
authors.initials: C
authors.lastname: Shang
authors.forename: Richard M
authors.initials: RM
authors.lastname: Chen
authors.forename: Pei
authors.initials: P
authors.lastname: Han
authors.forename: Jin
authors.initials: J
authors.lastname: Yang
authors.forename: Kryn
authors.initials: K
authors.lastname: Stankunas
authors.forename: Bingruo
authors.initials: B
authors.lastname: Wu
authors.forename: Minggui
authors.initials: M
authors.lastname: Pan
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.forename: Michael T
authors.initials: MT
authors.lastname: Longaker
authors.forename: Ching-Pin
authors.initials: CP
authors.lastname: Chang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D004265:DNA Helicases / Q000502:physiology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000293:injuries / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology* / Q000378:metabolism; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*; D000071676:Zinc Finger Protein GLI1
chemical_list: C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D016328:NF-kappa B; D009687:Nuclear Proteins; C509239:SHH protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D008156:Luciferases; C513194:Smarca4 protein, mouse; D004265:DNA Helicases