SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice.
SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice.
复制标题
SIRT7 激活静止的毛囊干细胞，以确保小鼠的毛发生长。
DOI：
10.15252/embj.2019104365
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发表时间：
2020-09-15
期刊：
影响因子：
--
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Li G;Tang X;Zhang S;Jin M;Wang M;Deng Z;Liu Z;Qian M;Shi W;Wang Z;Xie H;Li J;Liu B
毛囊干细胞（HFSC）维持在静止状态，直到激活生长，但重新激活静止HFSC水库的机制尚不清楚。在这里，我们发现小鼠中Sirt 7的缺失阻碍了毛囊从休止期到生长期的生命周期转变，导致毛发生长延迟。相反，在休止期Sirt 7过表达促进HSFC生长期的进入和加速头发生长。从机制上讲，Sirt 7在休止期到生长期的过渡期间在HFSC中上调，HFSC特异性Sirt 7敲除小鼠（Sirt 7 f/f;K15-Cre）表现出类似的毛发生长延迟。在分子水平上，Sirt 7与转录调节因子Nfatc 1在K612处相互作用并使其脱乙酰化，导致PA 28 γ依赖性蛋白酶体降解，以终止Nfatc 1介导的休止期静止并促进生长期进入。环孢素A是一种有效的钙调磷酸酶抑制剂，可抑制Nfatc 1的核滞留，消除毛囊周期延迟，并促进Sirt 7 −/−小鼠的毛发生长。此外，Sirt 7在老年HFSC中下调，外源性Sirt 7过表达促进老年动物的毛发生长。这些数据表明，Sirt 7通过使Nfatc 1不稳定来激活HFSC，以确保毛囊周期启动。皮肤干细胞活化和毛发周期起始由蛋白质脱乙酰酶Sirt 7控制。
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. Skin stem cell activation and hair cycle initiation are controlled by protein deacetylase Sirt7.
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