title: Hepatocyte-specific ablation in zebrafish to study biliary-driven liver regeneration.
abstract: The liver has a great capacity to regenerate. Hepatocytes, the parenchymal cells of the liver, can regenerate in one of two ways: hepatocyte- or biliary-driven liver regeneration. In hepatocyte-driven liver regeneration, regenerating hepatocytes are derived from preexisting hepatocytes, whereas, in biliary-driven regeneration, regenerating hepatocytes are derived from biliary epithelial cells (BECs). For hepatocyte-driven liver regeneration, there are excellent rodent models that have significantly contributed to the current understanding of liver regeneration. However, no such rodent model exists for biliary-driven liver regeneration. We recently reported on a zebrafish liver injury model in which BECs extensively give rise to hepatocytes upon severe hepatocyte loss. In this model, hepatocytes are specifically ablated by a pharmacogenetic means. Here we present in detail the methods to ablate hepatocytes and to analyze the BEC-driven liver regeneration process. This hepatocyte-specific ablation model can be further used to discover the underlying molecular and cellular mechanisms of biliary-driven liver regeneration. Moreover, these methods can be applied to chemical screens to identify small molecules that augment or suppress liver regeneration.
authors.affiliation: Department of Developmental Biology, McGowan Institute for Regenerative Medicine, University of Pittsburgh.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Choi
authors.affiliation: Department of Developmental Biology, McGowan Institute for Regenerative Medicine, University of Pittsburgh.
authors.forename: Mehwish
authors.initials: M
authors.lastname: Khaliq
authors.affiliation: Department of Developmental Biology, McGowan Institute for Regenerative Medicine, University of Pittsburgh.
authors.forename: Sungjin
authors.initials: S
authors.lastname: Ko
authors.affiliation: Department of Developmental Biology, McGowan Institute for Regenerative Medicine, University of Pittsburgh.
authors.forename: Juhoon
authors.initials: J
authors.lastname: So
authors.affiliation: Department of Developmental Biology, McGowan Institute for Regenerative Medicine, University of Pittsburgh; donghuns@pitt.edu.
authors.forename: Donghun
authors.initials: D
authors.lastname: Shin
mesh_terms: D055011:Ablation Techniques / Q000379:methods*; D000818:Animals; D030801:Animals, Genetically Modified; D001659:Biliary Tract / Q000166:cytology / Q000502:physiology*; D005260:Female; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008795:Metronidazole / Q000494:pharmacology; D023421:Models, Animal; D009601:Nitroreductases / Q000096:biosynthesis / Q000235:genetics; D015027:Zebrafish
chemical_list: D008795:Metronidazole; D009601:Nitroreductases