A rat liver cell atlas reveals intrahepatic myeloid heterogeneity

The large size and vascular accessibility of the laboratory rat (Rattus norvegicus) make it an ideal hepatic animal model for diseases that require surgical manipulation. Often, the disease susceptibility and out-comes of inflammatory pathologies vary significantly between strains. This study uses single-cell transcrip-tomics to better understand the complex cellular network of the rat liver, as well as to unravel the cellular and molecular sources of inter-strain hepatic variation. We generated single-cell and single-nucleus tran-scriptomic maps of the livers of healthy Dark Agouti and Lewis rat strains and developed a factor analysis -based bioinformatics analysis pipeline to study data covariates, such as strain and batch. Using this approach, we discovered transcriptomic variation within the hepatocyte and myeloid populations that un-derlie distinct cell states between rat strains. This finding will help provide a reference for future investi-gations on strain-dependent outcomes of surgical experiment models.