Dynamic remodeling of translation programs drives hepatocyte proliferation during liver regeneration

During liver regeneration, most new hepatocytes arise from pre-existing ones; yet, the underlying mechanisms that drive these cells from quiescence to proliferation remain poorly defined. By using high-resolution transcriptome profiling of polysome fractions from purified hepatocytes isolated from quiescent and toxin-injured adult mouse livers,we uncover the mRNA transcripts regulated during liver regeneration. The translational remodeling modulates protein levels of a set of splicing factors including Epithelial splicing regulatory protein 2 (ESRP2), which activates an early postnatal splicing program in regenerating hepatocytes as well as metabolic genes. Hepatocytes were isolated in presence of Cycloheximide (CHX) from normal fed mice and DDC fed (4 week) mice. Polysomal fractions were separated over sucrose gradient and RNA was isolated from the three fractions Monosome (1 ribosome), Light polysome (2-4 ribosomes) and Heavy polysomes (>5). Isolated RNA was subject to polyA selection and sequenced on an Illumina platform.