Distinct hepatocyte adaptations during gestation and lactation [pregnant_liver_mm10_CUT_RUN]

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. STAT3 CUT&RUN in G14.5 Il6st WT and KO hepatocytes, and H3K27ac CUT&RUN in P4-L Acss2 WT and KO hepatocytes.