In this episode, we are thrilled to have Dr. Morrisey join us as he sheds light on his groundbreaking research into the human lung's unique structure and its implications on diseases like chronic obstructive pulmonary disease (COPD).

The human lung's architecture is markedly different from that of mice, particularly in its distal airway configuration and its interplay with the alveolar gas-exchange niche, resulting in a unique anatomical structure known as the respiratory bronchioles. This uniqueness has largely left the cellular and molecular mechanisms governing respiratory bronchioles unexplored, owing to the lack of a counterpart in mice.

Dr. Morrisey and his team discovered a unique secretory cell population within the human respiratory bronchioles, distinct from those found in larger proximal airways. Through organoid modeling, they found that these Respiratory Airway Secretory (RAS) cells act as progenitors for Alveolar Type 2 cells, vital for maintaining and regenerating the alveolar niche. RAS cell differentiation into Alveolar Type 2 cells is influenced by Notch and Wnt signaling.

Importantly, the team noted that RAS cells transcriptionally change in cases of COPD, leading to abnormal Alveolar Type 2 cell states associated with smoking exposure in both humans and ferrets.

Join us as Dr. Morrisey elaborates on the implications of these findings, the role of the newly discovered RAS cells, and how this knowledge could transform our understanding and treatment of chronic lung diseases.

Keywords: Human lung, distal airway, alveolar gas-exchange niche, respiratory bronchioles, RAS cells, Alveolar Type 2 cells, Notch and Wnt signaling, COPD, organoid modeling, chronic lung disease.

https://doi.org/10.1038/s41586-022-04552-0 These data identify a distinct progenitor in a region of the human lung that is critical in maintaining the gas-exchange and altered in chronic lung disease.