Autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway

作者:Zeng, Jianxing; Jing, Yingying; Shi, Rongyu; Pan, Xiaorong; Lai, Fobao; Liu, Wenting; Li, Rong; Gao, Lu; Hou, Xiaojuan; Wu, Mengchao; Wei, Lixin*
来源:Cell Cycle, 2016, 15(12): 1602-1610.
DOI:10.1080/15384101.2016.1181234

摘要

Autophagy plays important roles in self-renewal and differentiation of stem cells. Hepatic progenitor cells (HPCs) are thought to have the ability of self-renewal as well as possess a bipotential capacity, which allows them to differentiate into both hepatocytes and bile ductular cells. However, how autophagy contributes to self-renewal and differentiation of hepatic progenitor cells is not well understood. In this study, we use a well-established rat hepatic progenitor cell lines called WB-F344, which is treated with 3.75mM sodium butyrate (SB) to promote the differentiation of WB-F344 along the biliary phenotype. We found that autophagy was decreased in the early stage of biliary differentiation, and maintained a low level at the late stage. Activation of autophagy by rapamycin or starvation suppressed the biliary differentiation of WB-F344. Further study reported that autophagy inhibited Notch1 signaling pathway, which contributed to biliary differentiation and morphogenesis. In conclusions, autophagy regulates biliary differentiation of hepatic progenitor cells through Notch1 signaling pathway.