Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence

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 human...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Nature (London) 2021-04, Vol.592 (7854), p.428-432
Hauptverfasser: Choi, Sekyu, Zhang, Bing, Ma, Sai, Gonzalez-Celeiro, Meryem, Stein, Daniel, Jin, Xin, Kim, Seung Tea, Kang, Yuan-Lin, Besnard, Antoine, Rezza, Amelie, Grisanti, Laura, Buenrostro, Jason D., Rendl, Michael, Nahrendorf, Matthias, Sahay, Amar, Hsu, Ya-Chieh
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. Stress inhibits  hair growth in mice through the release of the stress hormone corticosterone from the adrenal glands, which inhibits the activation of hair follicle stem cells by suppressing the expression of a secreted factor, GAS6, from the dermal niche.
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-021-03417-2