Genomic and epigenomic characterization of regenerating hepatocytes

To gain a deeper understanding of the genetic basis of liver repopulation after injury, we utilize an innovative technique to profile the expression changes and chromatin landscape during the regenerative response. We utilize the Fah-/- mouse, a model for hereditary tyrosinemia deficient in fumarylacetoacetate hydrolase (FAH), that undergoes repopulation with FAH-expressing hepatocytes. We employ translating ribosome affinity purification followed by RNA-sequencing (TRAP-seq) and assay for transposase accessible chromatin using sequencing (ATAC-seq) to specifically isolate regenerating hepatocytes and performed high-throughput sequencing to identify the dynamic genomic and epigenomic changes during liver repopulation. Overall design: A total of 16 mice was used for the TRAP-seq study (n=4, quiescent; n=3, 1-week injury; n=6, 4-week injury; n=3, 4-week severe injury). A total of 7 mice was used for the ATAC-seq study (n=2, quiescent; n=4, 1-week injury)