The liver serves as a central metabolic hub, essential for homeostasis, detoxification, and immunity. Recent advances in single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq) have fundamentally transformed our capacity to resolve the cellular architecture and functional states of this complex organ. This review comprehensively examines the pivotal applications and expanding potential of these high-resolution transcriptomic technologies in hepatic research, encompassing both established model organisms and emerging non-model species. In human and classical models such as mice and zebrafish, scRNA-seq and snRNA-seq have been critical for delineating developmental trajectories, deciphering the molecular logic of metabolic zonation, and uncovering the precise cellular dynamics and intercellular communication networks that drive diseases like non-alcoholic fatty liver disease (NAFLD), fibrosis, and hepatocellular carcinoma. Beyond these systems, pioneering work in species such as cattle, pigs, tree shrews, and reptiles is now providing unique insights into evolutionary adaptations, specialized physiologies, and comparative disease mechanisms. By synthesizing findings across this broad biological spectrum, we illustrate how single-cell transcriptomics is refining the core principles of liver biology while simultaneously revealing species-specific divergences. Looking ahead, the continued maturation and application of these technologies are poised to yield deeper comparative pathophysiological understanding and accelerate the development of targeted diagnostic and therapeutic strategies for liver diseases in both human and veterinary contexts.
Feng et al. (Mon,) studied this question.
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