Epithelial Plasticity during Liver Injury and Regeneration

• Published in: Cell stem cell Vol. 27; no. 4; pp. 557 - 573
• Main Authors: Gadd, Victoria L., Aleksieva, Niya, Forbes, Stuart J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-10-2020
• Subjects: biliary epithelial cell; Cell Proliferation; cell therapy; Epithelial Cells; hepatic progenitor cell; hepatocyte; Hepatocytes; Humans; lineage-tracing; Liver; Liver Diseases; Liver Regeneration; plasticity; reprogramming; transdifferentiation; reprogramming; hepatocyte; lineage-tracing; cell therapy; hepatic progenitor cell; transdifferentiation; plasticity; liver regeneration; biliary epithelial cell
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2020.08.016

Following injury, the liver’s epithelial cells regenerate efficiently with rapid proliferation of hepatocytes and biliary cells. However, when proliferation of resident epithelial cells is impaired, alternative regeneration mechanisms can occur. Intricate lineage-tracing strategies and experimental models of regenerative stress have revealed a degree of plasticity between hepatocytes and biliary cells. New technologies such as single-cell omics, in combination with functional studies, will be instrumental to uncover the remaining unknowns in the field. In this review, we evaluate the experimental and clinical evidence for epithelial plasticity in the liver and how this influences the development of therapeutic strategies for chronic liver disease.
A deeper understanding of the mechanisms controlling epithelial plasticity in the liver is crucial for the development of novel therapies for chronic liver diseases. Gadd et al. review the current knowledge in the field and comment on the remaining controversies and unknowns and how they might be resolved.