Ciliated epithelial cell lifespan in the mouse trachea and lung

Abstract

The steady-state turnover of epithelial cells in the lung and trachea is highly relevant to investigators who are studying endogenous stem cells, manipulating gene expression in vivo, or using viral vectors for gene therapy. However, the average lifetime of different airway epithelial cell types has not previously been assessed using currently available genetic techniques. Here, we use Cre/loxP genetic technology to indelibly label a random fraction of ciliated cells throughout the airways of a cohort of mice and follow them in vivo for up to 18 mo. We demonstrate that ciliated airway epithelial cells are a terminally differentiated population. Moreover, their average half-life of 6 mo in the trachea and 17 mo in the lung is much longer than previously available estimates, with significant numbers of labeled cells still present after 18 mo.

Fig. 1.

The percentage of lineage-labeled ciliated cells in the airways decreases over time. A–G: representative FOXJ1CreER^2T; Rosa26R-eYFP/+ frozen sections posttamoxifen. Green, anti-green fluorescent protein (GFP) (lineage label); red, anti-β-tubulin (cilia). A–E: trachea sections. F and G: terminal bronchiole sections. Bar = 50 μm in all panels.

Fig. 2.

The percentage change of lineage-labeled ciliated cells fits to a first-order exponential decay function. A–C: the data points are the mean percentage of lineage-labeled ciliated cells ± SE. Exponential decay functions (curves) were fitted to these data by regression analysis. Half-life of the ciliated cells was estimated from the fitted equations to be 6 mo in the trachea (A), 17 mo in the bronchioles (B), and 14 mo in the terminal bronchioles (C). D: plotting the natural log of the percentage of lineage-labeled ciliated cells against time converts the exponential curves to straight lines.