Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function

Aryl hydrocarbon receptor (AhR) is required for skin homeostasis and hair growth. AhR depletion in keratinocytes and dermal fibroblasts compromises skin regeneration likely because of reduced epidermal stem cells (EpdSCs) numbers. Reconstitution assays suggest a cell autonomous role for AhR in the epidermis. Signaling networks controlling skin homeostasis are AhR regulated in EpdSCs. AhR modulation by physiological ligands may represent a strategy to treat skin pathology. AbstractSkin 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 inAhR −/− mice delayed morphogenesis and impaired hair regrowth with a phenotype closely correlating with a reduction in suprabasal bulge stem cells ( α6lowCD34+). Moreover, RNA-microarray and RT-qPCR analyse...
Source: Stem Cells - Category: Stem Cells Authors: Tags: Tissue ‐Specific Stem Cells Source Type: research