title: Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis.
abstract: Mechanisms of plasticity to acquire different cell fates are critical for adult stem cell (SC) potential, yet are poorly understood. Reduced global histone methylation is an epigenetic state known to mediate plasticity in cultured embryonic SCs and T-cell progenitors. Here we find histone H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells (HFSCs) during G0 quiescence. The level of marks over specific gene promoters did not correlate to mRNA level changes in quiescent HFSCs. Skin hypomethylation during quiescence was necessary for subsequent progression of hair homeostasis (cycle). Inhibiting BMP signal, a known HFSC anti-proliferative factor, elevated HFSC methylation in vivo during quiescence prior to proliferation onset. Furthermore, removal of proliferation factors and addition of BMP4 reduced histone methylases and increased demethylases mRNAs in cultured skin epithelial cells. We conclude that signalling couples hair follicle stem cell quiescence with reduced H3 K4/K9/K27me3 levels for proper tissue homeostasis.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Jayhun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Sangjo
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Karin C
authors.initials: KC
authors.lastname: Lilja
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Keegan J
authors.initials: KJ
authors.lastname: Colletier
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Cornelia Johanna Franziska
authors.initials: CJ
authors.lastname: Scheitz
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Ying V
authors.initials: YV
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Tudorita
authors.initials: T
authors.lastname: Tumbar
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression; D006197:Hair / Q000166:cytology / Q000378:metabolism*; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006706:Homeostasis; D008297:Male; D008745:Methylation; D057507:Mice, 129 Strain; D008856:Microscopy, Fluorescence; D016192:Resting Phase, Cell Cycle; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D006657:Histones