Characterisation of a primary ciliary dyskinesia model generated from <i>BMI1</i> -transduced basal epithelial cells
Primary ciliary dyskinesia (PCD) is a rare genetic respiratory disorder caused by a reduction in cilia number or cilia 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 current models have limited potential of self-renewal in vitro. Here, we describe a human PCD cell model created by lentiviral transduction of airway basal epithelial cells with the 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 an air-liquid interface showed lower activity of the Na+ channel ENaC and enhanced CFTR activity compared to non-PCD cells, which might be linked to ciliary immotility. Our study provides a robust PCD model for therapeutic studies, opening new avenues to investigate the molecular mechanisms of this disease.
Authors
- Eriomina Shahaj (ORCID: https://orcid.org/0000-0001-5428-0405)
- Dani Do Hyang Lee (ORCID: https://orcid.org/0000-0002-2695-5759)
- Anna Straatman-Iwanowska (ORCID: https://orcid.org/0000-0001-8251-7668)
- Claire Hogg (ORCID: https://orcid.org/0000-0002-8368-5994)
- Hannah M. Mitchison (ORCID: https://orcid.org/0000-0002-3163-6293)
- Robert A. Hirst (ORCID: https://orcid.org/0000-0003-1989-1790)
- Deborah L. Baines (ORCID: https://orcid.org/0000-0001-7229-0244)
- Stephen L. Hart (ORCID: https://orcid.org/0000-0001-8254-376X)
- Melis T. Dalbay (ORCID: https://orcid.org/0000-0002-2691-5941)
- Christopher O’Callaghan (ORCID: https://orcid.org/0000-0002-8633-2473)
- Ileana Guerrini
Institutions
- University of Leicester (GB)
- St George's, University of London (GB)
- Royal Brompton & Harefield NHS Foundation Trust (GB)
- Institute of Child Health (IN)
- Institute of Infection and Immunity (CA)
- NIHR Leicester Biomedical Research Centre (GB)
- University College London (GB)
- Imperial College London (GB)
Publication Details
- Journal
- Journal of Cell Science
- Published
- 2025-10-09
- DOI
- https://doi.org/10.1242/jcs.263886
- Citations
- 1
- Primary Topic
- Cystic Fibrosis Research Advances
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- University of Dundee
- NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
- Newlife the Charity for Disabled Children
- National Institute for Health and Care Research
- University of Leicester
- Imperial College London
- University College London
- Great Ormond Street Hospital for Children