Fig. 1

Regeneration of pseudostratified airway epithelium of the lung. a The airways are lined by a pseudostratified epithelium consisting of secretory cells (goblet and club cells), ciliated cells, neuroendocrine cells and basal cells. Goblet cells are abundant in the human epithelium, but are rare in mice. b The relationship between the different epithelial cells during normal homeostasis. The basal cells are progenitor cells of the pseudostratified epithelium which are heterogeneous for the expression of Krt14. The basal cell becomes a Krt8 positive luminal precursor cell before further differentiation. A basal cell differentiate into secretory cells and neuroendocrine cells under homeostatic conditions. Neuroendocrine cells are also capable to self-renew [162]. Scgb1a1⁺ secretory cells are a self-renewing population and can give rise to ciliated cells. In homeostatic epithelium, there is a very low turnover of cells. It is likely that the dividing secretory cell population is sufficient to regenerate ciliated cells in homeostatic condition. However, their generation from basal cells is not excluded. Upon allergen exposure, secretory cells are the main source of goblet cells [163], but it is unknown whether basal cells can directly differentiate into goblet cells. (C). Upon depletion of luminal cells by SO₂exposure, basal cells proliferate and subdivide into two populations, N2ICD and c-myb positive, respectively, differentiating into secretory and ciliated cells. After the loss of basal cells, secretory cells (de)differentiate into functional progenitor basal stem cells. In a normal pseudostratified epithelium, only a few scattered goblet cells are present. Increases in goblet cells are observed upon immune stimuli and in diseases like COPD. Lineage tracing studies show that goblet cells can arise from Scgb1a1⁺ secretory cells and recently a trans-differentiation of foxj1⁺ ciliated cells to goblet cells was observed upon smoke exposure in culture