Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life‐cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen‐to‐anagen transition, and HFSC‐specific Sirt7 knockout mice (Sirt7^f/f;K15‐Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ‐dependent proteasomal degradation to terminate Nfatc1‐mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7^−/− mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.

中文翻译：

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SIRT7激活静止的毛囊干细胞，以确保小鼠的毛发生长。

毛囊干细胞（HFSC）保持静止状态直到被激活以生长，但是重新激活静止HFSC储库的机制尚不清楚。在这里，我们发现小鼠Sirt7的缺失会阻止毛囊生命周期从端源期到生长期转变，从而导致头发生长延迟。相反，在telogen期Sirt7的过表达促进了HSFC的生长期进入并加速了头发的生长。从机理上讲，在端粒-生长期过渡期间，HFSC中的Sirt7被上调，而HFSC特异性的Sirt7基因敲除小鼠（Sirt7 ^{f / f}; K15‐Cre）表现出相似的头发生长延迟。在分子水平上，Sirt7与K612的转录调节因子Nfatc1相互作用并使其脱乙酰基，导致PA28γ依赖性蛋白酶体降解终止Nfatc1介导的端粒静止并增强生长期。环孢菌素A（一种有效的钙调神经磷酸酶抑制剂）抑制Nfatc1的核保留，消除毛囊周期延迟，并促进Sirt7 ^-/-小鼠的毛发生长。此外，Sirt7在衰老的HFSC中被下调，而外源性Sirt7的过表达促进衰老动物的毛发生长。这些数据表明，Sirt7通过使Nfatc1不稳定来激活HFSC，以确保毛囊周期的启动。