PUBLICATION

A Temporal Map of Gene Expression Pattern During Zebrafish Liver Regeneration

Authors
Jagtap, U., Sivadas, A., Basu, S., Verma, A., Sivasubbu, S., Scaria, V., Sachidanandan, C.
ID
ZDB-PUB-191127-11
Date
2019
Source
Zebrafish   17(1): 1-10 (Journal)
Registered Authors
Jagtap, Urmila, Sachidanandan, Chetana, Sivasubbu, Sridhar
Keywords
MYC, cholesterol, liver, regeneration, temporal, transcriptomic, zebrafish
MeSH Terms
  • Animals
  • Chemical and Drug Induced Liver Injury/pathology
  • Female
  • Gene Expression/physiology*
  • Liver Regeneration/genetics*
  • Metronidazole/toxicity*
  • Transcriptome*
  • Zebrafish/genetics
  • Zebrafish/physiology*
PubMed
31770088 Full text @ Zebrafish
Abstract
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. In this study, 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. Analyzing these data, we find that soon after injury the immediate early transcription factor MYC induces a battery of genes that respond to the MTZ-induced ROS by activating oxido-reductase pathways and apoptosis machinery. Immediately after injury, liver cells downregulate many functional genes, including complement protein synthesis, bile acid, and lipid biosynthesis, in a concerted manner. At 6 days postinjury, we find a dramatic induction of cholesterol biosynthesis and protein folding machinery, with expression levels returning to predamage 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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping