A temporal map of gene expression pattern during zebrafish liver regeneration

Background & Aims: Zebrafish is increasingly being used to study liver injuryand regeneration. However, very little is known about molecular players that respond to injury and participate in liver regeneration. Here we aim to generate a temporal map of gene expression changes at injury and during regeneration of the adult zebrafish liver. Methods: We use a metronidazole- nitroreductase(MTZ-nfsb) based system to selectively ablate hepatocytes in adult zebrafish to create a model for liver injuryand regeneration. Through RNA sequencing of liver samples at multiple time points we generate a comprehensive temporal map of gene expression changes during injury and regeneration. Results: Gene expression reveals 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. Upon injury, liver cells down regulate genes encoding complement proteins, bile acid and lipid biosynthesis pathway in a concerted manner. Midway through regeneration, we discover a spike of cholesterol biosynthesis and protein folding machinery genes suggesting an important role for these pathways in liver regeneration. Conclusions: The temporal transcriptomic map of liver regenerationwould serve as a framework for further studies in understanding, and for screening for compounds that augment liver regeneration.