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Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice

Lrig1 is known to repress the epidermal growth through its inhibitory activity on EGFR, while CD44 promotes it. We analyzed the expression of these molecules in senescent atrophic human epidermis and in the epidermis of CD44KO mice. In normal human epidermis, Lrig1+ cells form clusters located in th...

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Autores principales: Barnes, Laurent, Saurat, Jean-Hilaire, Kaya, Gürkan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242443/
https://www.ncbi.nlm.nih.gov/pubmed/28099467
http://dx.doi.org/10.1371/journal.pone.0169452
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author Barnes, Laurent
Saurat, Jean-Hilaire
Kaya, Gürkan
author_facet Barnes, Laurent
Saurat, Jean-Hilaire
Kaya, Gürkan
author_sort Barnes, Laurent
collection PubMed
description Lrig1 is known to repress the epidermal growth through its inhibitory activity on EGFR, while CD44 promotes it. We analyzed the expression of these molecules in senescent atrophic human epidermis and in the epidermis of CD44KO mice. In normal human epidermis, Lrig1+ cells form clusters located in the basal layer in which CD44 expression is downregulated and Lef1 expression reflects an active Wnt signaling. In senescent atrophic human epidermis, we found retention of Lrig1(high)+ cells all along the basal layer, forming no clusters, with decrease of CD44 and lef1 expression. In vitro silencing of CD44 indicated that CD44 may be required for Wnt signaling. However, if looking at the ear epidermis of CD44KO mice, we only found a limited interfollicular epidermal atrophy and unchanged Lrig1(high)+ cells in the hair follicle. Cell lineage tracing further revealed that interfollicular epidermis did lost its self-renewing capacity but that its homeostasis relied on Lrig1-derived keratinocytes migrating from the hair follicle. Therefore, we conclude that CD44 downregulation is part of the phenotype of senescent atrophic human epidermis, and contributes to reduce Wnt signaling and to alter Lrig1(high)+ stem cell distribution.
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spelling pubmed-52424432017-02-06 Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice Barnes, Laurent Saurat, Jean-Hilaire Kaya, Gürkan PLoS One Research Article Lrig1 is known to repress the epidermal growth through its inhibitory activity on EGFR, while CD44 promotes it. We analyzed the expression of these molecules in senescent atrophic human epidermis and in the epidermis of CD44KO mice. In normal human epidermis, Lrig1+ cells form clusters located in the basal layer in which CD44 expression is downregulated and Lef1 expression reflects an active Wnt signaling. In senescent atrophic human epidermis, we found retention of Lrig1(high)+ cells all along the basal layer, forming no clusters, with decrease of CD44 and lef1 expression. In vitro silencing of CD44 indicated that CD44 may be required for Wnt signaling. However, if looking at the ear epidermis of CD44KO mice, we only found a limited interfollicular epidermal atrophy and unchanged Lrig1(high)+ cells in the hair follicle. Cell lineage tracing further revealed that interfollicular epidermis did lost its self-renewing capacity but that its homeostasis relied on Lrig1-derived keratinocytes migrating from the hair follicle. Therefore, we conclude that CD44 downregulation is part of the phenotype of senescent atrophic human epidermis, and contributes to reduce Wnt signaling and to alter Lrig1(high)+ stem cell distribution. Public Library of Science 2017-01-18 /pmc/articles/PMC5242443/ /pubmed/28099467 http://dx.doi.org/10.1371/journal.pone.0169452 Text en © 2017 Barnes et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Barnes, Laurent
Saurat, Jean-Hilaire
Kaya, Gürkan
Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice
title Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice
title_full Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice
title_fullStr Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice
title_full_unstemmed Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice
title_short Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice
title_sort senescent atrophic epidermis retains lrig1+ stem cells and loses wnt signaling, a phenotype shared with cd44ko mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242443/
https://www.ncbi.nlm.nih.gov/pubmed/28099467
http://dx.doi.org/10.1371/journal.pone.0169452
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