CD44highalveolar type II cells show stem cell properties during steady-state alveolar homeostasis

The alveolar epithelium is composed of type I cells covering most of the gas-blood exchange surface and type II cells secreting surfactant that lowers surface tension of alveoli to prevent alveolar collapse. Here, we have identified a subgroup of type II cells expressing a higher level of cell surface molecule CD44 (CD44 high type II cells) that composed ~3% of total type II cells in 5–10-wk-old mice. These cells were preferentially apposed to lung capillaries. They displayed a higher proliferation rate and augmented differentiation capacity into type I cells and the ability to form alveolar organoids compared with CD44 low type II cells. Moreover, in aged mice, 18–24 mo old, the percentage of CD44 high type II cells among all type II cells was increased, but these cells showed decreased progenitor properties. Thus CD44 high type II cells likely represent a type II cell subpopulation important for constitutive regulation of alveolar homeostasis.