Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
| Autor: | Angel Carlos Roman, Luis Francisco Lorenzo-Martín, Xosé R. Bustelo, Pedro M. Fernández-Salguero, Jaime M. Merino, Eva M. Rico-Leo |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), Ministerio de Ciencia, Innovación y Universidades (España), Junta de Extremadura, European Commission |
| Rok vydání: | 2021 |
| Předmět: |
Cellular differentiation
Receptor expression Morphogenesis Mice Nude Biology Quiescence Mice Hair cycle medicine Basic Helix-Loop-Helix Transcription Factors Cell differentiation Animals Homeostasis Regeneration Skin homeostasis Progenitor cell Hair follicle integumentary system Regeneration (biology) Stem Cells AhR Cell Biology Epidermal stem cells Cell biology medicine.anatomical_structure Receptors Aryl Hydrocarbon Molecular Medicine Stem cell Epidermis Developmental Biology |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | © 2021 The Authors. 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 (α6lowCD34+). 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. This work was supported by grants to P.M.F.S. from the Spanish Ministry of Economy and Competitiveness (SAF2017-82597-R and PID2020-114846RB-I00) and from the Junta de Extremadura (GR18006, IB160210, and IB20014). E.M.R.L. was supported by the RTICC and the Junta de Extremadura. All Spanish funding is cosponsored by the European Union FEDER program. |
| Databáze: | OpenAIRE |
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