A single-cell RNA sequencing study of human liver tissue reveals distinct intrahepatic macrophage populations. The liver is a critical organ for metabolism and immune function, but little is known about its cellular composition. This study provides a comprehensive map of the human liver's cellular landscape using single-cell RNA sequencing (scRNA-seq) on 8444 cells from five healthy liver donors. The study identifies 20 distinct cell populations, including hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, T cells, NK-like cells, and distinct intrahepatic macrophage populations. The findings highlight the presence of two distinct populations of liver resident macrophages with inflammatory and non-inflammatory/immunoregulatory functions. The study also reveals the zonation of hepatocytes based on their location within the liver, with different clusters showing enriched expression of genes associated with specific functions. The study provides a detailed description of the human liver's cellular composition and immune microenvironment, offering a foundation for understanding liver disease pathogenesis and treatment. The results suggest that the liver's immune cells are distributed in specific patterns, though many details remain unknown. The study also identifies distinct populations of endothelial cells, cholangiocytes, and hepatic stellate cells, as well as the presence of two distinct populations of liver resident macrophages. The findings provide a reference map of the human liver at single-cell resolution, which can be used to study liver disease and develop new treatments.A single-cell RNA sequencing study of human liver tissue reveals distinct intrahepatic macrophage populations. The liver is a critical organ for metabolism and immune function, but little is known about its cellular composition. This study provides a comprehensive map of the human liver's cellular landscape using single-cell RNA sequencing (scRNA-seq) on 8444 cells from five healthy liver donors. The study identifies 20 distinct cell populations, including hepatocytes, endothelial cells, cholangiocytes, hepatic stellate cells, B cells, T cells, NK-like cells, and distinct intrahepatic macrophage populations. The findings highlight the presence of two distinct populations of liver resident macrophages with inflammatory and non-inflammatory/immunoregulatory functions. The study also reveals the zonation of hepatocytes based on their location within the liver, with different clusters showing enriched expression of genes associated with specific functions. The study provides a detailed description of the human liver's cellular composition and immune microenvironment, offering a foundation for understanding liver disease pathogenesis and treatment. The results suggest that the liver's immune cells are distributed in specific patterns, though many details remain unknown. The study also identifies distinct populations of endothelial cells, cholangiocytes, and hepatic stellate cells, as well as the presence of two distinct populations of liver resident macrophages. The findings provide a reference map of the human liver at single-cell resolution, which can be used to study liver disease and develop new treatments.