Single-cell RNA sequencing reveals the cell landscape of a radiation-induced liver injury mouse model

Abstract

The mechanisms of radiation-induced liver injury (RILI) has not been fully elucidated so far. In the present study, a RILI mouse model was constructed by exposing the liver to a single dose of 30 Gy X-rays. Liver injuries consisting of liver function damage and histopathological variations were confirmed after 2 weeks. And then the cellular atlas of RILI liver was generated by profiling 9,641 ​cells isolated from X-ray irradiated mice livers and control ones from RILI mice model using single-cell RNA sequencing (scRNA-seq). Seven cell types were identified, including B cells, natural killer cells, T cells, macrophages/Küpffer cells/Dendritic cells (DC), neutrophils, endothelial cells, and hepatocyte. Although there was no significant difference of overall cell typing was observed between the Control and RILI groups, hepatocytes and macro/Küpffer/DC cell types were chosen for further functional exploration. Gene expression profiles and bioinformatics analysis of hepatocytes revealed that multiple metabolic related pathways were enriched in livers exposed to IR. These scRNA-seq data were confirmed in RILI liver samples via adipose staining. Besides, obviously varied M1-/M2-macrophages polarization was observed in RILI liver, which was in accordance with the enzyme linked immunosorbent assay (ELISA) results of IR-induced M2 to pro-inflammatory M1 macrophages transformation in mouse macrophage cell line Raw264.7. In addition, we predicted that several genes were found to differentially expressed during the process of macrophage polarization from M2 to M1 subtype. Overall, our study provides a cellular landscape of RILI at single-cell resolution that indicates the characteristics of hepatocytes and macrophages, which will contribute to investigate the novel therapeutic or preventive management for RILI.

Keywords

• Radiation induced liver injury
• Single-cell RNA sequencing
• Hepatocyte
• Macrophage