Abstract
Poster: 182LEF1 drives functional CFTR ionocyte differentiation from human airway gland progenitors
Journal of cystic fibrosis, Vol.25(Suppl 2), pp.90-91
09/2026
DOI: 10.1016/j.jcf.2026.07.213
Abstract
Pulmonary ionocytes are rare airway epithelial cells (∼0.5–1%) but account for approximately 50% of cystic fibrosis transmembrane conductance regulator (CFTR) expression in proximal airways. Their conserved association with airway submucosal glands (SMGs) across species suggests a shared developmental origin. We previously showed that overexpression (OE) of the Wnt signaling transcription factor lymphoid enhancer-binding factor 1 (LEF1) in mouse SMG progenitors promotes ionocyte specification and CFTR function. To advance translational application, we investigated whether LEF1 OE similarly drives ionocyte differentiation and functional chloride transport in human tracheal SMG progenitors (htSMGs).
htSMGs were transduced with lentiviral vectors expressing EGFP (control) or EGFP plus human LEF1. EGFP⁺ control and EGFP⁺ LEF1-overexpressing (LEF1OE) cells were isolated by flow cytometry and differentiated in parallel air–liquid interface (ALI) cultures. CFTR-mediated chloride transport was assessed using Ussing chambers, followed by immunofluorescence analysis for ionocyte and epithelial markers.
LEF1OE significantly increased ionocyte specification in htSMG-derived ALI cultures, as evidenced by increased BSND and FOXI1 expression. Enhanced ionocyte abundance correlated with increased CFTR expression and GlyH101-inhibitable chloride secretion relative to controls, demonstrating functional augmentation of ionocyte-dependent anion transport.
These findings demonstrate that LEF1-driven ionocyte specification is conserved in human SMG progenitors and results in functional enhancement of CFTR activity. Importantly, human SMG myoepithelial cells represent a renewable, tissue-resident progenitor population that can be directed toward an ionocyte fate, supporting their potential use in cell-based or regenerative therapeutic strategies aimed at restoring CFTR function in cystic fibrosis.
Details
- Title: Subtitle
- Poster: 182LEF1 drives functional CFTR ionocyte differentiation from human airway gland progenitors
- Creators
- W. Shahin - University of Iowa, Cardiothoracic SurgeryJ. Hajibabazade - University of IowaK. Campbell - University of Alabama at BirminghamJ. Engelhardt - University of Alabama at Birmingham
- Resource Type
- Abstract
- Publication Details
- Journal of cystic fibrosis, Vol.25(Suppl 2), pp.90-91
- DOI
- 10.1016/j.jcf.2026.07.213
- ISSN
- 1569-1993
- Publisher
- Elsevier B.V
- Number of pages
- 2
- Language
- English
- Date published
- 09/2026
- Academic Unit
- Anatomy and Cell Biology; Cardiothoracic Surgery
- Record Identifier
- 9985236323802771
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