Spatial single-cell omics: new insights into liver diseases

The liver is a highly multifunctional organ that can perform many metabolic and immunological functions due to a highly complex spatially organised microarchitecture that is disturbed in many liver diseases. Recent methodological advances in spatial omics technologies enable the comprehensive study of the intrahepatic proteome, transcriptome and metabolome at near single-cell and subcellular resolution. The spatial resolution adds an additional dimension to our understanding of the liver, with the potential to revolutionise our insights into the cellular and molecular mechanisms underlying liver physiology and their dysregulation in liver disease. The identification of spatial niches and interactions is empowered by advanced bioinformatics approaches facilitating spatial cellular and network-level analysis and providing novel opportunities for clinical translation. A recent example in immuno-oncology is the use of spatial architecture-based immune classifications, which can improve patient stratification. In this review, we provide an overview of the current methodology and novel spatial insights into metabolic, infectious, immune-mediated, toxic and malign liver diseases and discuss perspectives for clinical translation.