Protecting the lung from hypoxic stress The lung experiences constantly changing oxygen concentrations and must recognize and respond to a low-oxygen environment. Shivaraju et al. reveal that airway stem cells directly sense hypoxia and respond by differentiating into protective neuroendocrine (NE) cells that secrete a peptide that mitigates tissue damage (see the Perspective by Zacharias). This work suggests that the observed NE cell hyperplasia that accompanies lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease represents a compensatory physiologic response. More broadly, it raises the possibility that stem cells throughout the body sense hypoxia and differentiate into organ-specific NE cells. Science , this issue p. 52 ; see also p. 32