Clinical Assistant Professor Seoul National University Hospital, Republic of Korea
Abstract: Recent revolutionary advancements in transgenic mice and sequencing technologies allow us to extend our knowledge of lung diseases, including pulmonary fibrosis. However, considering the fundamental differences between human and mouse lungs, the validation of findings in humans is essential. Precision-cut lung slices (PCLS) culture, an ex vivo tissue culture technique, offers a significant advantage in preserving the spatial composition of the extracellular matrix, making it more useful for tracking epithelial-mesenchymal interactions in fibrosis. We recently developed and applied single-cell RNA sequencing, spatial transcriptomics, and a machine-learning-based fiber quantification algorithm to a mouse model of pulmonary fibrosis, identifying fibroblast subtypes with pro-fibrotic and pro-reparative roles. We also found that Pi16 and Serpine2, expressed in these fibroblasts, are important candidates. Here, we performed the validation of these proteins in a human PCLS model in an unbiased manner. Both conventional and machine-learning-based analyses showed that the roles of these proteins in human lungs are similar to those in mouse lungs. In the era of hypothesis-driven science, these approaches are becoming increasingly important.
