Decoding liver fibrogenesis with single-cell technologies

Liver fibrogenesis is a highly dynamic and complex process that drives the progression of chronic liver disease toward liver failure and end-stage liver diseases. Despite decades of intense studies, the cellular and molecular mechanisms underlying liver fibrogenesis remain elusive, and no approved therapies to treat liver fibrosis are currently available. The rapid development of single-cell RNA sequencing (scRNA-seq) technologies allows the characterization of cellular alterations under healthy and diseased conditions at an unprecedented resolution. In this Review, we discuss how the scRNA-seq studies are transforming our understanding of the regulatory mechanisms of liver fibrosis. We specifically emphasize discoveries on disease-relevant cell subpopulations, molecular events, and cell interactions on cell types including hepatocytes, liver sinusoidal endothelial cells, myofibroblasts, and macrophages. These discoveries have uncovered critical pathophysiological changes during liver fibrogenesis. Further efforts are urged to fully understand the functional contributions of these changes to liver fibrogenesis, and to translate the new knowledge into effective therapeutic approaches.