Dalbay, Melis T;
Shahaj, Eriomina;
Guerrini, Ileana;
Lee, Dani Do Hyang;
Straatman-Iwanowska, Anna;
Mitchison, Hannah M;
Baines, Deborah L;
... Hart, Stephen L; + view all
(2025)
Characterisation of primary ciliary dyskinesia model generated from BMI1 transduced basal epithelial cells.
Journal of Cell Science
, Article jcs.263886. 10.1242/jcs.263886.
(In press).
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Abstract
Primary ciliary dyskinesia (PCD) is a rare genetic respiratory disorder, caused by a reduction in cilia number or dysmotility. Cilia dysmotility leads to breathing difficulties, concurrent infections and severe lung damage if not treated, with no therapies currently available. Improved airway epithelial cell models, that mimic the disease phenotype, are required for development of new therapeutics, as they exert limited potential of self-renewal in vitro. Here we describe a human PCD cell model by lentiviral transduction of airway basal epithelial cells with BMI1 gene, a regulator of senescence. We report that the cells retain their proliferation and differentiation capacity for at least 19 passages and recapitulate the disease phenotype with immotile cilia lacking DNAH5 and other outer dynein arm proteins. Characterisation of the ion transport properties of these PCD cells grown at air-liquid interface showed lower activity of the sodium channel ENaC and enhanced CFTR activity compared to non-PCD cells, which may be linked to ciliary immotility. Our study provides a robust PCD model for therapeutic studies and may open new avenues to investigate the molecular mechanisms of this disease.
| Type: | Article |
|---|---|
| Title: | Characterisation of primary ciliary dyskinesia model generated from BMI1 transduced basal epithelial cells |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1242/jcs.263886 |
| Publisher version: | https://doi.org/10.1242/jcs.263886 |
| Language: | English |
| Additional information: | © 2025. Published by The Company of Biologists 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 that the original work is properly attributed. |
| Keywords: | Airway cell culture models, ENaC, PCD |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10215840 |
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