Delineating the hierarchy of lung progenitor cells and their response to influenza.

Influenza viruses are significant human respiratory pathogens that cause acute inflammation and widespread epithelial cell death in the lungs [1]. Yet, patients can recover, even after widespread destruction of epithelial cells, implying that the lung has a tremendous capacity for regeneration after injury. The mechanism by which this wound-healing process occurs remains unclear. In the adult mouse lung, current models of lung repair have established that different cell types participate in the wound-healing response depending on the nature, anatomical region of the lung (tracheobronchial airways, bronchiolar airways or the alveoli) and extent of the injury. Basal cells are the main stem cell population in the tracheobronchial airways, club cells serve as abundant progenitors in the bronchiolar airways, and type II cells support the maintenance of the alveoli. There is also convincing evidence for the existence of a multipotent stem cell population(s) that can give rise to both airway and alveolar lineages, but the precise identity of these stem cells and their response to lung injury remains unclear [2, 3]. Thus, a key question remains: are rare stem cell populations aroused from their quiescent state to participate in de novo tissue regeneration after extensive epithelial injury?