The best laid schemes of airway repair.

Schemes of homeostasis and repair The mouse trachea is lined by basal, secretory and ciliated cells. Previous genetic lineage tracing studies have shown that in the homeostatic and repairing mouse trachea, basal cells are widespread, multipotent progenitor cells capable of both long-term self-renewal and differentiation into ciliated and secretory cells [3, 4]. Similar experiments have also shown that differentiated tracheal club cell (Clara cell) secretory protein (CCSP)expressing cells can also self renew and give rise to ciliated cells, but that these do not play a major role in tracheal homeostasis [5]. In a recent publication, TATA et al. [1] found that murine airways exhibit an unexpected cellular plasticity in response to genetically mediated basal progenitor cell ablation. Lineage labelling showed that tracheal CCSP-expressing cells can differentiate into fully functional basal cells competent to act as epithelial progenitors. This alternate strategy of CCSP-expressing cell-mediated repair of the tracheal epithelium was also replicated in vitro, suggesting that contact-mediated signalling between airway basal cells and CCSP-expressing cells is required to prevent CCSP-expressing cells dedifferentiating to basal progenitor cells in homeostatic airways. The Notch and Egfr intercellular signalling pathways, or those of other surface receptors, such as cadherins, are candidates to mediate such a signal [6–8].