期刊
CELL CYCLE
卷 15, 期 12, 页码 1602-1610出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2016.1181234
关键词
autophagy; biliary differentiation; hepatic progenitor cells; Notch1
类别
资金
- Key Basic Research Project of China [2012CBA01303]
- National Natural Science Foundation of China [81372312, 81472737, 81402018, 81402020, 81401308, 81402026, 81372330, 81572444, 81502417, 81502543]
- Special Funds for National Key Sci-Tech Special Project of China [2012ZX10002-016, 2012ZX10002011-011]
- Shanghai Science and Technology Committee [14ZD1900403, 14ZR1409200, 15PJ1410600]
- Shanghai Municipal Education Commission [14ZZ086]
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.
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