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

© 2021 The Authors.

Detalles Bibliográficos
Autores: Rico-Leo, Eva M., Lorenzo-Martín, L. Francisco, Román, Ángel C., Bustelo, Xosé R., Merino, Jaime, Fernández-Salguero, Pedro M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/261120
Acceso en línea:http://hdl.handle.net/10261/261120
Access Level:acceso abierto
Palabra clave:AhR
Cell differentiation
Epidermal stem cells
Hair follicle
Quiescence
Regeneration
Skin homeostasis
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spelling Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell functionRico-Leo, Eva M.Lorenzo-Martín, L. FranciscoRomán, Ángel C.Bustelo, Xosé R.Merino, JaimeFernández-Salguero, Pedro M.AhRCell differentiationEpidermal stem cellsHair follicleQuiescenceRegenerationSkin homeostasis© 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.Oxford University PressMinisterio de Economía y Competitividad (España)Agencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)Junta de ExtremaduraEuropean CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/261120reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-82597-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114846RB-I00http://dx.doi.org/10.1002/stem.3443Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2611202026-05-22T06:33:51Z
dc.title.none.fl_str_mv Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
title Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
spellingShingle Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
Rico-Leo, Eva M.
AhR
Cell differentiation
Epidermal stem cells
Hair follicle
Quiescence
Regeneration
Skin homeostasis
title_short Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
title_full Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
title_fullStr Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
title_full_unstemmed Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
title_sort Aryl hydrocarbon receptor controls skin homeostasis, regeneration, and hair follicle cycling by adjusting epidermal stem cell function
dc.creator.none.fl_str_mv Rico-Leo, Eva M.
Lorenzo-Martín, L. Francisco
Román, Ángel C.
Bustelo, Xosé R.
Merino, Jaime
Fernández-Salguero, Pedro M.
author Rico-Leo, Eva M.
author_facet Rico-Leo, Eva M.
Lorenzo-Martín, L. Francisco
Román, Ángel C.
Bustelo, Xosé R.
Merino, Jaime
Fernández-Salguero, Pedro M.
author_role author
author2 Lorenzo-Martín, L. Francisco
Román, Ángel C.
Bustelo, Xosé R.
Merino, Jaime
Fernández-Salguero, Pedro M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Agencia Estatal de Investigación (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Junta de Extremadura
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv AhR
Cell differentiation
Epidermal stem cells
Hair follicle
Quiescence
Regeneration
Skin homeostasis
topic AhR
Cell differentiation
Epidermal stem cells
Hair follicle
Quiescence
Regeneration
Skin homeostasis
description © 2021 The Authors.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/261120
url http://hdl.handle.net/10261/261120
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2017-82597-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-114846RB-I00
http://dx.doi.org/10.1002/stem.3443
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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