Human PSC-based Modeling of Pulmonary Fibrosis Identifies p300/CBP Inhibition as a Suppressor of Alveolar Transitional Cell State [epithelial]

In this study, we conducted a drug screening using an in vitro pulmonary fibrosis model and identified p300/CBP inhibitors as candidate therapeutic agents. We investigated the mechanisms underlying the emergence of the alveolar transitional cell state (ATCS) with human PSC-derived alveolar organoids. Overall design: Alveolar organoids composed of SPC-GFP reporter iPSC line (B2-3)-derived alveolar epithelial cells and human fetal lung fibroblasts (HFLFs) were treated with DMSO or BLM for 3 days, followed by an additional 3-day incubation with or without compounds. For gene expression profile analysis, epithelial cells were isolated from the organoids through magnetic activated cell sorting (MACS) using anti-EpCAM antibody.