Regeneration is defined as the functional and anatomical regrowth of an injured organ. Unlike most human organs, the liver exhibits the remarkable capacity to regenerate. The process of liver regeneration is multifaceted, as it requires a complex tissue comprised of multiple cell types to sense the extent of injury and mount an appropriate compensatory regrowth response.
In this work we have established a novel model of liver injury in zebrafish, known as cryoinjury, that will enable a thorough characterization of the mechanistic underpinnings of liver regeneration. Importantly, the cryoinjury model is focal in nature, which enables an exploration of clonality in the context of adjacent uninjured tissue. Bulk RNA-seq analysis of uninjured and injured livers revealed an adaptive regenerative response in the liver upon cryoinjury. Importantly, these transcriptional programs were restored to homeostasis as the regenerative process reached completion. We have also developed a tissue clearing pipeline coupled to confocal microscopy that enabled us to follow the phenotypic changes that occur during liver regeneration at cellular resolution. As clonal diversity is essential to understand regenerative processes, we are developing a novel method to study lineage clonality using a single cell barcoding based approach. In summary, we have established a new focal liver injury model in the zebrafish that recapitulates aspects of acute liver failure.
In the future, we hope that this model will provide the foundation to a better understanding of molecular and cellular mechanisms regulating regeneration.