A temporal map of gene expression pattern during zebrafish liver regeneration.

Zebrafish is increasingly being used to study liver injury and regeneration. However, very little is known about molecular players that respond to injury and those important for liver regeneration. We use a metronidazole-nitroreductase (MTZ-nfsb) based system to selectively ablate hepatocytes in adult zebrafish to create a model for liver injury and regeneration. Here, we generate a comprehensive temporal map of gene expression changes during regeneration through RNA sequencing of liver samples at various stages of injury and regeneration. Analysing this data, we find that soon after injury the immediate early transcription factor MYC induces a battery of genes that respond to the metronidazole-induced ROS by activating oxido-reductase pathways and apoptosis machinery. Immediately after injury, liver cells down regulate many functional genes including complement protein synthesis, bile acid and lipid biosynthesis, in a concerted manner. At 6 days post injury, we find a dramatic induction of cholesterol biosynthesis and protein folding machinery, with expression levels returning to pre-damage levels by 8 days, suggesting an important role for these pathways in liver regeneration. This chronological transcriptomic map of liver regeneration in zebrafish would serve as a framework for further studies in understanding, and for screening for compounds that augment liver regeneration.