Distinct hepatocyte adaptations during gestation and lactation [pregnant_liver_mm10]

Using high-resolution single-cell RNA sequencing, we systematically characterized hepatocyte adaptations in mice across pregnancy and postpartum stages. We discovered a cyclical hepatocyte trajectory (“pregnancy clock”) governing metabolic changes during gestation and postpartum recovery, which reverted to pregestational states in non-lactating mice. Lactation induced a distinct branching trajectory characterized by elevated lipid synthesis and export. Deletion of gp130 disrupted hepatic adaptations during pregnancy, impairing fetal growth, whereas ACSS2 deficiency postpartum disrupted lipid export, affecting milk quality and offspring growth. Overall design: To comprehensively investigate hepatocyte state transitions throughout gestational (G) and postpartum (P) periods, we isolated single hepatocytes from maternal C57BL/6J mice mated at approximately 8 weeks of age. Single-cell RNA sequencing (scRNA-seq) was conducted across continuous reproductive stages, encompassing both lactating (L) and non-lactating (NL) phases.