Abstract
The hepatic mesenchyme has been studied extensively in the context of liver fibrosis; however, much less is known regarding the role of mesenchymal cells during liver regeneration. As our knowledge of the cellular and molecular mechanisms driving hepatic regeneration deepens, the key role of the mesenchymal compartment during the regenerative response has been increasingly appreciated. Single-cell genomics approaches have recently uncovered both spatial and functional zonation of the hepatic mesenchyme in homeostasis and following liver injury. Here we discuss how the use of preclinical models, from in vivo mouse models to organoid-based systems, are helping to shape our understanding of the role of the mesenchyme during liver regeneration, and how these approaches should facilitate the precise identification of highly targeted, pro-regenerative therapies for patients with liver disease.