Transcriptomics and single cell sequencing revealed the important role of PPAR signaling pathway in zebrafish liver fibrosis induced by thioacetamide.

Thioacetamide (TAA) is widely used in agricultural, industrial, and pharmaceutical products, which can cause serious damage to the body through inhalation or ingestion. The liver is the main target organ of TAA accumulation, and the fibrotic damage of TAA to the liver has been widely confirmed. However, the underlying mechanism is complex and unclear. In this study, we first successfully constructed a model of liver fibrosis by exposing zebrafish to TAA. Through transcriptomic sequencing, we found that the peroxisome proliferator-activated receptor (PPAR) signaling pathway is involved in the progression of liver fibrosis. Then, the key cell subpopulations and regulatory mechanisms of liver fibrosis were analyzed by single-cell sequencing, and the PPAR signaling pathway was also screened. Finally, the sequencing results were verified by intervention experiment. Overall, our results offer a powerful resource for studying intercellular interactions, signaling pathways, and regulators in liver fibrosis, the PPAR signaling pathway may be an effective target.