Genome-wide CRISPR Screening to Identify Drivers of TGF-β-Induced Liver Fibrosis in Human Hepatic Stellate Cells
Shan Yu, Matthew Ericson, Andrea Fanjul, Derek M. Erion, Maria D. Paraskevopoulou, Erin N. Smith, Banumathi K. Cole, Ryan E. Feaver, Corine Holub, Narender R. Gavva, Shane R. Horman, Jie Huang
Abstract
Liver fibrosis progression in chronic liver disease leads to cirrhosis, liver failure, or hepatocellular carcinoma and often ends in liver transplantation. Even with an increased understanding of liver fibrogenesis and many attempts to generate therapeutics specifically targeting fibrosis, there is no approved treatment for liver fibrosis. To further understand and characterize the driving mechanisms of liver fibrosis, we developed a high-throughput genome-wide CRISPR/Cas9 screening platform to identify hepatic stellate cell (HSC)-derived mediators of transforming growth factor (TGF)-β-induced liver fibrosis. The functional genomics phenotypic screening platform described here revealed the novel biology of TGF-β-induced fibrogenesis and potential drug targets for liver fibrosis.