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  3. 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

  • EMBO J. 2020 Sep 15;39(18):e104365. doi: 10.15252/embj.2019104365.
Guo Li  # 1,  Xiaolong Tang  # 2 3,  Shuping Zhang 1,  Meiling Jin 4,  Ming Wang 2 3,  Zhili Deng 1,  Zuojun Liu 2 3,  Minxian Qian 2 3,  Wei Shi 1,  Zimei Wang 2 3,  Hongfu Xie 1,  Ji Li 1 5 6 7,  Baohua Liu 2 3 8
Affiliations

Affiliations

  • 1 Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  • 2 Shenzhen Key Laboratory for Systemic Aging and Intervention (SAI), National Engineering Research Center for Biotechnology (Shenzhen), International Cancer Center, Shenzhen University, Shenzhen, China.
  • 3 Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Department of Biochemistry & Molecular Biology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, China.
  • 4 CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 5 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  • 6 Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, Hunan, China.
  • 7 Department of Dermatology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
  • 8 Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen, China.
  • # Contributed equally.
PMID: 32696520 DOI: 10.15252/embj.2019104365
Abstract

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 (SIRT7f/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.

Keywords

Nfatc1; PA28γ; Sirt7; aging; hair follicle stem cells.

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