Nfatc1 orchestrates aging in hair follicle stem cells
Nfatc1 orchestrates aging in hair follicle stem cells
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DOI：
10.1073/pnas.1320301110
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发表时间：
2013-12-17
影响因子：
11.1
通讯作者：
Fuchs, Elaine
中科院分区：
文献类型：
--
作者：
Keyes, Brice E.;Segal, Jeremy P.;Fuchs, Elaine
头发的产生是由干细胞（SC）推动的，干细胞在周期性的休息和活动之间过渡。在这里，我们探讨为什么头发生长随着年龄的增长而减弱。我们发现，老年毛囊干细胞（HFSCs）在小鼠中表现出增强的休息和缩短的生长阶段，并延迟响应组织再生的线索。老化的HFSC在启动增殖方面较差，并且在广泛使用时显示出降低的自我更新能力。只有适度恢复联体，这些功能是植根于升高的细胞内在的敏感性和骨形态发生蛋白（BMP）信号的局部升高。转录谱呈现与老化HFSC激活缺陷一致的差异。值得注意的是，BMP-/钙调节，活化T细胞c1（NFATc 1）在HFSCs的核因子变得异常，其正常的下调线索，NFATc 1 ChIP测序分析揭示了显着富集NFATc 1靶基因内的年龄相关的签名。此外，当BMP和/或NFATc 1被抑制时，老化的HFSC显示出更年轻的毛发再生水平。这些结果为皮肤SC如何老化提供了独特的见解。
Hair production is fueled by stem cells (SCs), which transition between cyclical bouts of rest and activity. Here, we explore why hair growth wanes with age. We show that aged hair follicle SCs (HFSCs) in mice exhibit enhanced resting and abbreviated growth phases and are delayed in response to tissue-regenerating cues. Aged HFSCs are poor at initiating proliferation and show diminished self-renewing capacity upon extensive use. Only modestly restored by parabiosis, these features are rooted in elevated cell-intrinsic sensitivity and local elevation in bone morphogenic protein (BMP) signaling. Transcriptional profiling presents differences consistent with defects in aged HFSC activation. Notably, BMP-/calcium-regulated, nuclear factor of activated T-cell c1 (NFATc1) in HFSCs becomes recalcitrant to its normal down-regulating cues, and NFATc1 ChIP-sequencing analyses reveal a marked enrichment of NFATc1 target genes within the age-related signature. Moreover, aged HFSCs display more youthful levels of hair regeneration when BMP and/or NFATc1 are inhibited. These results provide unique insights into how skin SCs age.