title: Senescent Atrophic Epidermis Retains Lrig1+ Stem Cells and Loses Wnt Signaling, a Phenotype Shared with CD44KO Mice.
abstract: 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 Lrig1high+ 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 Lrig1high+ 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 Lrig1high+ stem cell distribution.
authors.affiliation: Department of Dermatology, University Hospital of Geneva, University of Geneva, Geneva, Switzerland.
authors.forename: Laurent
authors.initials: L
authors.lastname: Barnes
authors.affiliation: Swiss Center for Applied Human Toxicology, University of Geneva, Geneva, Switzerland.
authors.forename: Jean-Hilaire
authors.initials: JH
authors.lastname: Saurat
authors.affiliation: Department of Dermatology, University Hospital of Geneva, University of Geneva, Geneva, Switzerland.
authors.forename: Gürkan
authors.initials: G
authors.lastname: Kaya
mesh_terms: D000818:Animals; D001284:Atrophy / Q000235:genetics; D004817:Epidermis / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: C497483:CD44 protein, human; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; C101671:Lrig1 protein, mouse; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C541485:EGFR protein, mouse; D066246:ErbB Receptors