Genome-wide CRISPR Screening to Identify Drivers of TGF-beta-Induced Liver Fibrosis in Human Hepatic Stellate Cells br

Liverfibrosis progression in chronic liver disease leads tocirrhosis, liver failure, or hepatocellular carcinoma and often ends in livertransplantation. Even with an increased understanding of liverfibrogenesisand many attempts to generate therapeutics specifically targetingfibrosis,there is no approved treatment for liverfibrosis. To further understand andcharacterize the driving mechanisms of liverfibrosis, we developed a high-throughput genome-wide CRISPR/Cas9 screening platform to identifyhepatic stellate cell (HSC)-derived mediators of transforming growth factor(TGF)-beta-induced liverfibrosis. The functional genomics phenotypicscreening platform described here revealed the novel biology of TGF-beta-inducedfibrogenesis and potential drug targets for liver fibrosis.