Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis.
Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis.
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DOI：
10.1038/ncomms11278
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发表时间：
2016-04-15
影响因子：
16.6
通讯作者：
Tumbar T
中科院分区：
文献类型：
--
作者：
Lee J;Kang S;Lilja KC;Colletier KJ;Scheitz CJ;Zhang YV;Tumbar T
获得不同细胞命运的可塑性机制对成体干细胞（SC）的潜力至关重要，但了解甚少。降低的整体组蛋白甲基化是已知介导培养的胚胎SC和T细胞祖细胞中的可塑性的表观遗传状态。在这里，我们发现组蛋白H3 K4/K9/K27 me 3水平在成年小鼠皮肤和毛囊干细胞（HFSC）在G 0静止期积极减少。在静止期HFSC中，特异性基因启动子标记的水平与mRNA水平的变化无关。静止期的皮肤低甲基化是随后毛发稳态（周期）进展所必需的。抑制BMP信号，一种已知的HFSC抗增殖因子，在增殖开始之前的静止期期间提高了体内HFSC甲基化。此外，在培养的皮肤上皮细胞中，去除增殖因子和添加BMP 4降低了组蛋白甲基化酶并增加了去甲基化酶mRNA。我们的结论是，信号夫妇毛囊干细胞静止与减少H3 K4/K9/K27 me 3水平适当的组织稳态。 整体组蛋白三甲基化的变化与胚胎干细胞可塑性有关，但与成体干细胞可塑性无关。在这里，Lee等人发现H3 K4/K9/K27 me 3水平在静止期（退化期）的成年小鼠皮肤和毛囊干细胞中主动降低，并将其与活性骨形态发生蛋白信号传导联系起来。
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.