Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence

Sekyu Choi, Bing Zhang, Sai Ma, Meryem Gonzalez-Celeiro, Daniel Stein, Xin Jin, Seung Tea Kim, Yuan Lin Kang, Antoine Besnard, Amelie Rezza, Laura Grisanti, Jason D. Buenrostro, Michael Rendl, Matthias Nahrendorf, Amar Sahay, Ya Chieh Hsu

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

Chronic, sustained exposure to stressors can profoundly affect tissue homeostasis, although the mechanisms by which these changes occur are largely unknown. Here we report that the stress hormone corticosterone—which is derived from the adrenal gland and is the rodent equivalent of cortisol in humans—regulates hair follicle stem cell (HFSC) quiescence and hair growth in mice. In the absence of systemic corticosterone, HFSCs enter substantially more rounds of the regeneration cycle throughout life. Conversely, under chronic stress, increased levels of corticosterone prolong HFSC quiescence and maintain hair follicles in an extended resting phase. Mechanistically, corticosterone acts on the dermal papillae to suppress the expression of Gas6, a gene that encodes the secreted factor growth arrest specific 6. Restoring Gas6 expression overcomes the stress-induced inhibition of HFSC activation and hair growth. Our work identifies corticosterone as a systemic inhibitor of HFSC activity through its effect on the niche, and demonstrates that the removal of such inhibition drives HFSCs into frequent regeneration cycles, with no observable defects in the long-term.

Original languageEnglish
Pages (from-to)428-432
Number of pages5
JournalNature
Volume592
Issue number7854
DOIs
StatePublished - 15 Apr 2021
Externally publishedYes

ASJC Scopus subject areas

  • General

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