Insight into Tetrabromobisphenol A-Associated Liver Transcriptional Landscape via Single Cell RNA Sequencing

Yunmeng Bai, Zhou Zhu, Jinhuan Ou, Wenqiao Zhang, Ashok Iyaswamy, Yuke Jiang, Jigang Wang*, Wei Zhang*, Chuanbin Yang*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

In recent years, there has been growing concern over the rising incidence of liver diseases, with increasing exposure to environmental toxins as a significant contributing factor. However, the mechanisms of liver injury induced by environmental pollutants are largely unclear. Here, using tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant, as an example, environmental toxin-induced liver toxicity in mice is characterized via single-cell sequencing technology. Heterogeneous gene expression profiles after exposure to TBBPA in major cell types of the liver are demonstrated. In hepatocytes, pathway analysis of differentially expressed genes reveals the enhanced interferon response and diminished metabolic processes. The disrupted endothelial functions in TBBPA-treated cells are then shown. Moreover, the activation of M2-polarization in Kupffer cells, as well as activated effector T and B cells are unveiled in TBBPA-treated cells. Finally, ligand-receptor pair analysis shows that TBBPA disrupts cell-cell communication and induces an inflammatory microenvironment. Overall, the results reveal that TBBPA-induced dysfunction of hepatocytes and endothelial cells may then activate and recruit other immune cells such as Kuffer cells, and T/NK cells into the liver, further increasing inflammatory response and liver injury. Thus, the results provide novel insight into undesiring environmental pollutant-induced liver injury.

Original languageEnglish
Article number2300477
JournalAdvanced Biology
DOIs
Publication statusE-pub ahead of print - 22 Oct 2023

Scopus Subject Areas

  • Biomaterials
  • Biomedical Engineering
  • Biochemistry, Genetics and Molecular Biology(all)

User-Defined Keywords

  • liver diseases
  • single-cell RNA sequencing
  • tetrabromobisphenol A
  • tissue immune inflammation

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