Regenerative properties of epithelial stem cells in the proximal airway

Mammalian airways are maintained and repaired by various epithelial stem cell populations that reside within them. Chronic respiratory diseases (CRDs), including chronic obstructive pulmonary disease (COPD) and asthma, trigger alterations to the cellular composition and physiology of the airway epithelial tissues. These alterations tend to progress the disease even further, and prevent the airways from performing essential cellular repair. Unfortunately, CRDs account for a significant portion of the global population’s morbidities and mortalities. Many of these diseases have no known cures, and the treatments available give only temporary symptomatic relief.

Lung epithelial stem cells present an intriguing and promising opportunity for next-generation CRD therapies. Targeting these populations of stem cells with genetic or pharmacologic therapeutics would allow for more effective and longer lasting treatments. These kinds of therapies, however, will require a more complete understanding of the basic mechanisms behind airway stem cell function and behavior. The research presented here is focused around the stem cells residing within the larger proximal airways. We demonstrate the importance of two different proteins, Lef-1 and Sox9, on the regulation of proximal airway epithelial stem cells. We show that each protein is involved in regulating stem cell proliferation, as well as the regenerative properties of these stem cells. Proteins are one of the primary drivers of cell function and tissue homeostasis, thus these findings directly benefit the ongoing work being done to discover new CRD therapies.