Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis

• Published in: Nature communications 2016-04, Vol.7 (1), p.11278-11278, Article 11278
• Main Authors: Lee, Jayhun, Kang, Sangjo, Lilja, Karin C., Colletier, Keegan J., Scheitz, Cornelia Johanna Franziska, Zhang, Ying V., Tumbar, Tudorita
• Format: Article
• Language: English
• Subjects: 13/100; 13/31; 14/63; 631/136/532/2443; 631/337/100/2285; 631/443/319/1557; 631/80/86; 64/60; 82/51; 96/1; Animals; Animals, Newborn; Blotting, Western; Bone Morphogenetic Proteins - metabolism; Cell division; Cells, Cultured; Epigenetics; Female; Follicles; Gene Expression; Genomes; Hair - cytology; Hair - metabolism; Hair Follicle - cytology; Hair Follicle - metabolism; Histones - metabolism; Homeostasis; Humanities and Social Sciences; Male; Methylation; Mice, 129 Strain; Microscopy, Fluorescence; multidisciplinary; Resting Phase, Cell Cycle; Reverse Transcriptase Polymerase Chain Reaction; Science; Science (multidisciplinary); Signal Transduction; Skin - cytology; Skin - metabolism; Stem cells; Stem Cells - cytology; Stem Cells - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms11278

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. Changes in global histone trimethylation have been linked to embryonic but not adult stem cell plasticity. Here, Lee et al . find H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells during quiescence (catagen) and link this to active bone morphogen protein signalling.