| Experiment Id | GSE102580 | Name | A single cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte |
| Experiment Type | RNA-Seq | Study Type | Baseline |
| Source | GEO | Curation Date | 2024-07-11 |
| description | The functions of epithelial tissues are dictated by the types, abundance, and distribution of the differentiated cells they contain. Attempts to restore tissue function after damage require knowledge of how physiological tasks are distributed among cell types, and how cell states vary between homeostasis, injury/repair, and disease. In the conducting airway, a heterogeneous basal cell population gives rise to specialized luminal cells that perform mucociliary clearance. We performed single cell profiling of human bronchial epithelial cells and mouse tracheal epithelial cells to obtain a comprehensive picture of cell types in the conducting airway and their behavior in homeostasis and regeneration. Our analysis reveals cell states that represent known and novel cell populations, delineates their heterogeneity, and identifies distinct differentiation trajectories during homeostasis and tissue repair. Finally, we identified a novel, rare cell type, which we call the "pulmonary ionocyte", that co-expresses FOXI1, multiple subunits of the V-ATPase, and CFTR, the gene mutated in cystic fibrosis (CF). Using immunofluorescence, signaling pathway modulation, and electrophysiology, we show that Notch signaling is necessary and FOXI1 expression sufficient to drive the production of the pulmonary ionocyte, and that the pulmonary ionocyte is a major source of CFTR activity in the conducting airway epithelium. Single-cell mRNA sequencing of: a) primary mouse upper airway epithelial cells under homeostasis and in a recovery time course following polidocanol induced injury (14,163 cells); b) human bronchial epithelial cells (HBECs) growns in an air-liquid interface (ALI) culture (2,970 cells); c) HBECs transduced with GFP (9,436 cells) or GFP:FOXI1 (10,330 cells) and grown in an ALI culture. |
