The alveolar stem cell niche of the mammalian lung

The alveolar region of the mammalian lung evolved to enable highly efficient gas exchange between the millions of air-filled sacs known as alveoli and blood circulating through the pulmonary vessels. Each alveolus is composed of epithelial and mesenchymal populations; Type 1 (AT1) and Type 2 (AT2) epithelial cells line the sacs while the mesenchymal compartment is composed of endothelial cells, pericytes, several different fibroblast subpopulations, and immune cells. Compared with organs such as the intestine and skin, there is normally little cell turnover in the adult lung. However, if the alveolar epithelium is damaged, for example, by toxic agents or viral infections, or if a lung lobe is removed, there is extensive repair or compensatory regrowth (neoalveolarization) of the tissue. It is now well accepted that AT2s function as epithelial stem cells for the alveoli, capable of long-term self-renewal and differentiation into AT1s. However, many important questions remain, in particular, about the functional heterogeneity of AT2s and how the different components of their local environment or niche interact to regulate their proliferation and differentiation. Known signaling factors include ligands and antagonists of the WNT, FGF, EGF and bone morphogenetic (BMP) signaling pathways as well as cytokines produced by immune cells. The relative contribution of these factors to alveolar homeostasis, repair and regrowth is discussed.

Duke Scholars

Author Brigid L. M. Hogan Cell Biology