Single-cell characterization of loss of mouse Protocadherin-1, a gene for airway hyperresponsiveness
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Le résumé fourni par la source
Asthma is a heterogeneous airway disease. We previously identified PCDH1 as a susceptibility gene for airway hyperresponsiveness (AHR), a hallmark of asthma. PCDH1 is an adhesion molecule, highly expressed in the airway epithelium. However, its role in AHR, airway inflammation, and remodeling are not fully understood. Using a Pcdh1-deficient mouse model, we tested whether Pcdh1 loss increases AHR and causes inflammation and airway remodeling at baseline or upon challenge with house dust mite (HDM). Naïve Pcdh1-knockout (KO) mice displayed higher AHR compared to heterozygous (HET) littermates, and lower lung compliance compared to wildtype (WT) littermate controls. Air-liquid interface (ALI) culture of tracheal epithelial cells revealed reduced barrier function in cultures from KO or HET compared to WT mice. Intriguingly, single-cell RNA-sequencing analysis of tracheal epithelial cells revealed higher proportions of basal cells and a unique hillock-like cell population in KO mice, while ciliated cells were lower in proportion. Interestingly, keratinization genes were higher expressed in basal, club, and ciliated cells from KO mice than from WT controls. Upon HDM exposure, Pcdh1-KO mice showed a greater increase in AHR compared to WT mice. Altogether, this study demonstrates that Pcdh1 deficiency in mice results in loss of airway epithelial barrier integrity and increased AHR at baseline and after HDM exposure. These changes are accompanied by alterations in airway epithelial differentiation as captured in scRNA-seq results. We conclude that Pcdh1-deficient mice recapitulate key features of asthma, and can be used to further study the critical molecular mechanisms of the disease.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Single-cell characterization of loss of mouse Protocadherin-1, a gene for airway hyperresponsiveness
- Date Crossref
- 27/09/2025
- Éditeur
- European Respiratory Society
- Type
- proceedings-article
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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University Medical Center Groningen pays non établi dans la noticeÉtablissement de santé
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University of Groningen Beatrix Children’s Hospital pays non établi dans la noticeUniversité ou école supérieure
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Ghent University pays non établi dans la noticeUniversité ou école supérieure
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Vlaams Instituut voor Biotechnologie pays non établi dans la noticeStructure de recherche
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VIB-UGent Center for Inflammation Research pays non établi dans la noticeStructure de recherche
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Faculty of Medicine and Health Sciences Department of Human Structure and Repair pays non établi dans la noticeUniversité ou école supérieure
University Medical Center Groningen, Beatrix Children’s Hospital — University of Groningen et Ghent University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.