Dysregulated alveolar epithelial cell progenitor function and identity in Hermansky-Pudlak syndrome.

Hermansky-Pudlak syndrome (HPS) is a genetic disorder of endosomal protein trafficking associated with pulmonary fibrosis in specific subtypes, including HPS-1 and HPS-2. Single mutant HPS1 and HPS2 mice display increased fibrotic sensitivity while double mutant HPS1/2 mice exhibit spontaneous fibrosis with aging, which has been attributed to HPS mutations in alveolar epithelial type II (AT2) cells. We utilized HPS mouse models and human lung tissue to investigate mechanisms of AT2 cell dysfunction driving fibrotic remodeling in HPS.

An injury-induced mesenchymal-epithelial cell niche coordinates regenerative responses in the lung.

Severe lung injury causes airway basal stem cells to migrate and outcompete alveolar stem cells, resulting in dysplastic repair. We found that this "stem cell collision" generates an injury-induced tissue niche containing keratin 5 epithelial cells and plastic Pdgfra mesenchymal cells. Single-cell analysis revealed that the injury-induced niche is governed by mesenchymal proliferation and Notch signaling, which suppressed Wnt/Fgf signaling in the injured niche.

Artificial intelligence-driven automated lung sizing from chest radiographs.

Lung size measurements play an important role in transplantation, as optimal donor-recipient size matching is necessary to ensure the best possible outcome. Although several strategies for size matching are currently used, all have limitations, and none has proven superior. In this pilot study, we leveraged deep learning and computer vision to develop an automated system for generating standardized lung size measurements using portable chest radiographs to improve accuracy, reduce variability, and streamline donor/recipient matching.