Tejus Walia

Helios Scholar

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by the formation of scar tissue within the lungs. In healthy lung there are three major alveolar cell types: flat and elliptical AT1 cells which are mainly responsible for gas exchange, cuboidal AT2 cells which act as alveolar stem cells differentiating into AT1 cells after damage, and transitional AT2 cells which exhibit intermediate characteristics of AT2 and AT1 cells. In IPF, damage to AT1 cells happens early in disease onset contributing to the repair response. In the context of disease or injury, the transition from AT2 to AT1 cells can be irregular leading to the formation of KRT5-/KRT17+ cells. Despite having a baseline understanding of the morphologies of these cells, there is inadequate information on the continuum of cell shape across these cell trajectories and whether there are any molecular changes associated with shape change. Using the 10X Genomics Xenium platform we profiled expression of 343 genes at subcellular resolution from 3 unaffected and 14 IPF samples. We found circularity differences among cell types and disease states, an association between cell shape in KRT5-/KRT17+ cells and histological features, and associations of genes relating to cell adhesion and binding with cell shape across all cell types and disease states. Understanding the molecular and morphological features of epithelial cells in IPF can lead to improvements in diagnostic accuracy, treatment strategies, and patient outcomes.