Stem Cell Niches in the Lung

In the context of homeostasis, cellular turnover in the airways of the lung is very low. Following injury, however, the lung can undergo dramatic regeneration and repair, which is imparted by region-specific stem/progenitor cells residing in distinct niches along the proximal-to-distal axis of the airway tree. Each niche has unique biologic characteristics, and controls the specification of lung stem/progenitor cells in proportion to the type and degree of injury. Evidence for the existence of physiologically and spatially distinct stem/progenitor cell populations in the mouse lung comes from in vivo lineage tracing experiments in genetically engineered mice, and from in vitro and ex vivo analyses in which phenotypic markers were used to isolate distinct stem/progenitor cell populations. Distinct, region-specific stem cell types in the mouse airway include basal-like cells in the ducts of submucosal glands (SMGs), basal cells in intercartilaginous regions of the proximal trachea and bronchi, variant club cells (formerly termed Clara cells) in the neuroendocrine bodies (NEBs) of bronchioles, bronchioalveolar stem cells (BASCs) at bronchioalveolar duct junctions (BADJs) in the respiratory bronchioles, and alveolar type II cells in the alveolar space. In this chapter, we review recent findings regarding the identification and isolation of region-specific stem/progenitor cells and properties of their niches in the lung.