Effects of TP63 Mutations on Keratinocyte Adhesion and Migration
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Le résumé fourni par la source
The goal of this study was to investigate the molecular mechanisms responsible for the formation of skin erosions in patients affected by Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC). This ectodermal dysplasia is caused by mutations in the TP63 gene, which encodes several transcription factors that control epidermal development and homeostasis. We generated induced pluripotent stem cells (iPSC) from AEC patients and corrected the TP63 mutations using genome editing tools. Three pairs of the resulting conisogenic iPSC lines were differentiated into keratinocytes (iPSC-K). We identified a significant downregulation of key components of hemidesmosomes and focal adhesions in AEC iPSC-K compared to their gene-corrected counterparts. Further, we demonstrated reduced iPSC-K migration, suggesting the possibility that a process critical for cutaneous wound healing might be impaired in AEC patients. Next, we generated chimeric mice expressing a TP63-AEC transgene and confirmed a downregulation of these genes in transgene-expressing cells in vivo. Finally, we also observed these abnormalities in AEC patient skin. Our findings suggest that integrin defects in AEC patients might weaken the adhesion of keratinocytes to the basement membrane. We propose that reduced expression of extracellular matrix adhesion receptors, potentially in conjunction with previously identified desmosomal protein defects, contribute to skin erosions in AEC.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Effects of TP63 Mutations on Keratinocyte Adhesion and Migration
- Date Crossref
- 05/05/2023
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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East Carolina University pays non établi dans la noticeUniversité ou école supérieure
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St. Louis Children's Hospital pays non établi dans la noticeÉtablissement de santé
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Brody School of Medicine Department of Biochemistry and Molecular Biology pays non établi dans la noticeUniversité ou école supérieure
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Illinois Dermatology Institute pays non établi dans la noticeStructure de recherche
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Washington University School of Medicine Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
East Carolina University, St. Louis Children's Hospital et Department of Biochemistry and Molecular Biology — Brody School of Medicine, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.