Delineation of biliary epithelial cell dynamics in maternal liver during pregnancy

Abstract

In pregnant mice, the maternal liver expands drastically during gestation, which is believed to be essential to accommodate various metabolic demands caused by physiological changes and fetal growth. Although hepatocyte proliferation and hypertrophy have been reported, little is known about the dynamics of biliary epithelial cells (BECs), which comprise the bile duct epithelium in the liver. Here, we show that BECs transiently proliferate during the early stage of gestation. Lineage tracing revealed that BEC progeny were retained in the bile duct epithelium and did not differentiate into hepatocytes, indicating BEC self-replication during pregnancy. RNA-sequencing analysis of BECs identified their early pregnancy-signature transcriptomes, which highlighted Yes-associated protein (YAP) signaling-related genes. Nuclear accumulation of YAP was enhanced in BECs during pregnancy but was barely detectable in hepatocytes. In addition, the pharmacological inhibition of YAP attenuated BEC proliferation and liver weight gain during pregnancy. Our results delineate the proliferation and transcriptomic dynamics of BECs during pregnancy and suggest the relevance of YAP-mediated signals.

Keywords: YAP; biliary epithelial cells; cell proliferation; liver; pregnancy.