# Human iPSC-based Modeling of Pulmonary Fibrosis Reveals p300/CBP Inhibition Suppresses Alveolar Transitional Cell State

## TL;DR

Using human iPSCs, researchers found that inhibiting p300/CBP reduces fibrotic cell states in a model of pulmonary fibrosis.

## Contribution

The study identifies p300/CBP inhibitors as potential therapeutic agents for pulmonary fibrosis.

## Key findings

- p300/CBP inhibitors suppress the alveolar transitional cell state in iPSC-derived alveolar organoids.
- Multi-omics analysis confirmed compatibility of the model with human IPF profiles.
- The findings suggest a new therapeutic target for treating pulmonary fibrosis.

## Abstract

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive scarring of lung tissue with an urgent need for effective treatments. Studies have shown that the alveolar transitional cell state (ATCS) emerges in fibrotic regions of the IPF lung. However, whether ATCS is the cause or consequence of fibrosis is controversial, and no therapeutic agents targeting the alveolar epithelial differentiation are used to treat IPF. In this study, we performed a drug screening with an in vitro pulmonary fibrosis model using fibroblast-dependent alveolar organoids derived from human induced pluripotent stem cells (iPSCs) and identified p300/CBP inhibitors as candidate therapeutic agents. Multi-omics technology revealed that ATCS induced from human iPSCs-derived alveolar organoids had a compatible profile with that reported in IPF and p300/CBP inhibitors suppressed the emergence of ATCS. Overall, these results elucidate the biological mechanisms of pulmonary fibrosis and provide a potential therapeutic target.

There are limited effective treatments for pulmonary fibrosis. Here, the authors demonstrate that p300/CBP inhibition in human iPSC–derived lung organoids suppresses fibrotic phenotypes and abnormal alveolar epithelial cell states.