The secretory and multiciliated cells of the adult lung are constantly replenished by multipotent epithelial progenitors: the basal cells. Basal cells give rise to parabasal intermediate progenitors, which then terminally differentiate into ciliated or secretory cells. However, the specific molecular mechanisms governing the production of parabasal cells in the lung remain mysterious. Using genetic and pharmacological approaches in air-liquid interface cultures of adult airway progenitors, Wellington Cardoso and colleagues (p. ) find that selective activation of Notch 3 identifies parabasal cells and controls the balance between basal and parabasal progenitor cells in airways. The authors show that Jagged 1 and 2 in basal cells are crucial for activation of Notch 3 signalling and for the generation of the pool of parabasal cells. Notably, individuals with chronic obstructive pulmonary disease were found to exhibit Notch 3 hypo-activation and an expanded basal progenitor pool. This work helps to unravel the precise molecular determinants regulating the airway progenitor pools, that are crucial for lung homeostasis.
