Maintenance and repair of the bronchiolar epithelium

Bronchioles of the distal conducting airway are lined by a simple epithelium composed primarily of nonciliated secretory (Clara) cells and ciliated cells. These cells are long-lived in the normal lung; renewal is mediated by cells that constitute a nonclassical stem cell hierarchy. Within this type of hierarchy, facultative progenitor cells are responsible for normal epithelial maintenance and rare adult tissue-specific stem cells are activated only in response to depletion of the facultative progenitor cell pool. This organizational structure is a departure from the classical stem cell hierarchies that maintain rapidly renewing tissues such as the epithelium of the small intestine. This article compares cellular and molecular mechanisms of epithelial renewal in the relatively quiescent bronchiolar epithelium and in the mitotically active intestinal epithelium. Fundamental distinctions between stem cell hierarchies of slowly and rapidly renewing epithelia are highlighted and may provide insight into tissue-specific interpretation of signals that mediate repair in some tissues but lead to remodeling and chronic disease in other organ systems.