Zeng Jianxing, Jing Yingying, Shi Rongyu, Pan Xiaorong, Lai Fobao, Liu Wenting, Li Rong, Gao Lu, Hou Xiaojuan, Wu Mengchao, Wei Lixin
a Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University , Shanghai , China.
c Fujian Medical University , Fuzhou , Fujian , China.
Cell Cycle. 2016 Jun 17;15(12):1602-10. doi: 10.1080/15384101.2016.1181234. Epub 2016 Jun 3.
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 3.75 mM 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.
自噬在干细胞的自我更新和分化中发挥着重要作用。肝祖细胞（HPCs）被认为具有自我更新能力以及双潜能，这使其能够分化为肝细胞和胆管细胞。然而，自噬如何促进肝祖细胞的自我更新和分化尚不清楚。在本研究中，我们使用一种成熟的大鼠肝祖细胞系WB-F344，用3.75 mM丁酸钠（SB）处理以促进WB-F344沿胆管表型分化。我们发现，在胆管分化早期自噬减少，在后期维持在低水平。雷帕霉素或饥饿激活自噬会抑制WB-F344的胆管分化。进一步研究表明，自噬抑制Notch1信号通路，该通路有助于胆管分化和形态发生。总之，自噬通过Notch1信号通路调节肝祖细胞的胆管分化。
