Wnt antagonist SFRP3 inhibits the differentiation of mouse hepatic progenitor cells

Wnt信号通路 祖细胞 生物 敌手 祖细胞 干细胞 细胞生物学 受体 信号转导 遗传学
作者
Yang Bi,Jiayi Huang,Yun He,Guoqiang Zhu,Yuxi Su,Bai‐Cheng He,Jinyong Luo,Yi Wang,Qi Kang,Qing Luo,Liang Chen,Guowei Zuo,Wei Jiang,Bo Liu,Qiong Shi,Min Tang,Bingqiang Zhang,Yaguang Weng,Aiping Huang,Lan Zhou,Tao Feng,Hue H. Luu,Rex C. Haydon,Tong‐Chuan He,Ni Tang
出处
期刊:Journal of Cellular Biochemistry [Wiley]
卷期号:108 (1): 295-303 被引量:82
标识
DOI:10.1002/jcb.22254
摘要

Abstract Wnt/β‐catenin pathway plays an important role in regulating embryonic development. Hepatocytes differentiate from endoderm during development. Hepatic progenitor cells (HPCs) have been isolated from fetal liver and extrahepatic tissues. Most current studies in liver development and hepatic differentiation have been focused on Wnts, β‐catenin, and their receptors. Here, we sought to determine the role of Wnt antagonists in regulating hepatic differentiation of fetal liver‐derived HPCs. Using mouse liver tissues derived from embryonic day E12.5 to postnatal day (PD) 28, we found that 13 of the 19 Wnt genes and almost all of Wnt receptors/co‐receptors were expressed in most stages. However, Wnt antagonists SFRP2, SFRP3, and Dkk2 were only detected in the early stages. We established and characterized the reversible stable HPCs derived from E14.5 mouse fetal liver (HP14.5). HP14.5 cells were shown to express high levels of early liver progenitor cell markers, but low levels or none of late liver markers. HP14.5 cells were shown to differentiate into mature hepatocytes upon dexamethasone (Dex) stimulation. Dex‐induced late marker expression and albumin promoter activity in HP14.5 cells were inhibited by exogenous expression of SFRP3. Furthermore, Dex‐induced glycogen synthesis of PAS‐positive HP14.5 cells was significantly inhibited by SFRP3. Therefore, our results have demonstrated that the expression of Wnt antagonists decreases as hepatic differentiation progresses, suggesting that a balanced Wnt signaling may be critical during mouse liver development and hepatic differentiation. J. Cell. Biochem. 108: 295–303, 2009. © 2009 Wiley‐Liss, Inc.
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