LISTA: LIver Spatio-Temporal Atlas

The liver is one of the largest organs in mammals and performs fundamental body functions. Despite its regular histological structure, hepatic cell responses in homeostasis and perturbation are yet poorly understood. This is due to the difficulty of systematically studying the characteristics and crosstalk of multiple cell types in different cell states and locations, some of which are transient. Here, we used Stereo-seq (Spatio-Temporal Enhanced REsolution Omics-sequencing) combined with high-throughput single-cell transcriptomic analysis to profile murine liver homeostasis and regeneration after partial resection. Our integrative analysis dissects with unprecedented resolution the transcriptomic gradients controlling liver cell function at the whole lobe scale, carefully defining how genes and gene regulatory networks are modulated through intercellular communication. Among other important regulators, we identified the transcriptional cofactor TBL1XR1 as an inflammation-induced master switch derepressing genes necessary for hepatocyte proliferation. Our work lays the foundation for future high-definition and tissue scale spatiotemporal studies of organ physiology and malfunction.