Temporal Analyses of Postnatal Liver Development and Maturation by Single Cell Transcriptomics

The liver is the largest metabolic organ in mammals to process most nutrients and cellular wastes, although its development and maturation in postnatal life is unclear. We performed single cell RNA-sequencing (scRNA-seq) analysis focusing on postnatal development and maturation of murine liver. A total of 52,834 single cell transcriptomes, collected from the newborn to adult livers, were analyzed. We observed dramatic changes in cellular compositions during liver postnatal development. We characterized the process of hepatocytes and sinusoidal endothelial cell zonation establishment at single cell resolution. Furthermore, trajectory and gene regulatory analyses showed development of circadian clock in early liver as well as response of several critical metabolic pathways in order to adapt to the abrupt environmental changes at birth and in the postnatal life. Finally, we identified a special type of macrophages, enriched at postnatal day 7, with hybrid phenotype of both macrophage and endothelial cells. Cell-cell interaction analysis indicated this group of cells involved in regulation of liver sinusoidal vascularization and Treg cell activity. This study provides a comprehensive blueprint for further dissection of liver functions and diseases. Overall design: Hepatic cells were isolated from wildtype C57BL/6 livers, at postnatal day 1, 3, 7, 21 and 56 (indicated by D1, D3, D7, D21, and D56, respectively).