Open AccessAryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
Author(s) -
RicoLeo Eva María,
LorenzoMartín Luis Francisco,
Román Ángel Carlos,
Bustelo Xosé Ramón,
Merino Jaime María,
FernándezSalguero Pedro María
Publication year - 2021
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.3443
Subject(s) - biology , hair follicle , stem cell , microbiology and biotechnology , aryl hydrocarbon receptor , progenitor cell , regeneration (biology) , adult stem cell , cellular differentiation , stem cell marker , hair cycle , immunology , transcription factor , genetics , gene
Skin integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. While interfollicular epidermal progenitors control normal homeostasis, hair follicle stem cells residing within the bulge provide regenerative potential during hair cycle and in response to wounding. The aryl hydrocarbon receptor (AhR) modulates cell plasticity and differentiation and its overactivation results in severe skin lesions in humans. However, its physiological role in skin homeostasis and hair growth is unknown. Reconstitution assays grafting primary keratinocytes and dermal fibroblasts into nude mice and 3‐D epidermal equivalents revealed a positive role for AhR in skin regeneration, epidermal differentiation, and stem cell maintenance. Furthermore, lack of receptor expression in AhR−/− mice delayed morphogenesis and impaired hair regrowth with a phenotype closely correlating with a reduction in suprabasal bulge stem cells (α6 low CD34 + ). Moreover, RNA‐microarray and RT‐qPCR analyses of fluorescence‐activated cell sorting (FACS)‐isolated bulge stem cells revealed that AhR depletion impaired transcriptional signatures typical of both epidermal progenitors and bulge stem cells but upregulated differentiation markers likely compromising their undifferentiated phenotype. Altogether, our findings support that AhR controls skin regeneration and homeostasis by ensuring epidermal stem cell identity and highlights this receptor as potential target for the treatment of cutaneous pathologies.