Open AccessGenome-wide CRISPR Screening to Identify Drivers of TGF-β-Induced Liver Fibrosis in Human Hepatic Stellate Cells
Author(s) -
Shan Yu,
Matthew Ericson,
Andrea Fanjul,
Derek M. Erion,
Maria D. Paraskevopoulou,
Erin N. Smith,
Banumathi K. Cole,
Ryan E. Feaver,
Corine Holub,
Narender Gavva,
Shane R. Horman,
Jie Huang
Publication year - 2022
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.2c00006
Subject(s) - hepatic stellate cell , cirrhosis , liver transplantation , fibrosis , hepatocellular carcinoma , hepatic fibrosis , chronic liver disease , cancer research , biology , liver fibrosis , liver disease , phenotype , medicine , pathology , transplantation , gene , genetics
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.