SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice.

The EMBO Journal
Guo LiBaohua Liu

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.

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Citations

Aug 18, 2020·The EMBO Journal·Matthew SimonVera Gorbunova
Dec 6, 2020·Experimental Dermatology·Seon A LeeTudorita Tumbar
Mar 20, 2021·Briefings in Functional Genomics·Andromachi Pouikli, Peter Tessarz
Jun 16, 2021·Open Biology·Ming TangWei-Guo Zhu
Jun 18, 2021·World Journal of Stem Cells·Xi-Min HuKun Xiong
Oct 12, 2021·Cell Transplantation·Xiaoshuang ZhangHongwu Du

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Methods Mentioned

BETA
transgenic
FACS
pull down
acetylation
ubiquitination
PCR
transfection
transfections
Assay
electrophoresis

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Pro Plus
Prism
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Excel
ImageJ
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