scRNAseq and TCRseq of hepatic and splenic CD8T cells from normal diet fed (ND), HFHC diet fed (HFHC), and resolution induced (RES) mice.

To explore key features associated with the resolution process in liver fibrosis, we here applied a unique murine model, in which mice were fed HFHC diet for 24 weeks, and then continued with the HFHC diet (HFHC) or switched to a normal diet (RES) for 5 weeks. We noted that both the frequency and number of intrahepatic CD8+ T cells remained significantly high in RES mice compared to normal diet-fed mice (ND). To reveal the transcriptome profiling-based subtypes of CD8+T cells present during the liver fibosis resolution, we performed scRNA-seq analysis. Total of 25851 cells were clustered into 17 clusters based on the gene signatures. We revealed CD69+CD103-CD8+ Trm cell enrichment in fibrosis resolution livers. scTCR-seq analysis further revealed the clonal enrichment mainly in the Cd44+Sell-S1pr1- liver Trm fractions. In addition, TCR clonotypes enriched in liver CD8+ Trm cells of RES mice were expanded compared to those in liver CD8+ T cells of ND mice, and rarely detected in spleen CD8+ T cells. mRNA and TCR repatoire profiles of liver CD8T cells derived from 35weeks old WT, HFHC, or RES mice.