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SIRT 7 activates quiescent hair follicle stem cells to ensure hair growth in mice
Author(s) -
Li Guo,
Tang Xiaolong,
Zhang Shuping,
Jin Meiling,
Wang Ming,
Deng Zhili,
Liu Zuojun,
Qian Minxian,
Shi Wei,
Wang Zimei,
Xie Hongfu,
Li Ji,
Liu Baohua
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019104365
Subject(s) - biology , hair follicle , hair growth , microbiology and biotechnology , stem cell , medicine , endocrinology , physiology
Hair follicle stem cells ( HFSC s) 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 HFSC s 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 PA 28γ‐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 HFSC s, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSC s by destabilizing Nfatc1 to ensure hair follicle cycle initiation.