Role of β-catenin in development of bile ducts
Role of β-catenin in development of bile ducts
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DOI：
10.1016/j.diff.2016.02.001
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发表时间：
2016-01-01
期刊：
影响因子：
2.9
通讯作者：
Lemaigre, Frederic P.
中科院分区：
文献类型：
--
作者：
Cordi, Sabine;Godard, Cecile;Lemaigre, Frederic P.
已知β-连环蛋白在肝脏发育过程中发挥阶段特异性和细胞特异性功能。然而，其在胆管发育中的作用尚未得到解决。在这里，我们使用阶段特异性的体内功能获得和丧失方法，以及小鼠中的谱系追踪实验，首先证明β-连环蛋白是肝前体细胞（成肝细胞）分化为胆管细胞前体的关键。第二，当β-连环蛋白在后者中耗尽时，胆管细胞的成熟、胆管形态发生和门静脉周围肝细胞从胆管细胞前体的分化是正常的。相比之下，稳定的β-连环蛋白在胆管细胞前体扰动导管的发展和胆管细胞分化。我们的结论是β-连环蛋白是胆汁的发展，但它的活动必须保持在严格的限制。我们的工作有望对干细胞体外分化为胆管细胞产生重大影响，用于毒理学研究和疾病建模。(C)2016年国际分化学会。Elsevier B. V.出版，保留所有权利。
Beta-catenin is known to play stage- and cell-specific functions during liver development. However, its role in development of bile ducts has not yet been addressed. Here we used stage-specific in vivo gain-and loss-of-function approaches, as well as lineage tracing experiments in the mouse, to first demonstrate that beta-catenin is dispensable for differentiation of liver precursor cells (hepatoblasts) to cholangiocyte precursors. Second, when beta-catenin was depleted in the latter, maturation of cholangiocytes, bile duct morphogenesis and differentiation of periportal hepatocytes from cholangiocyte precursors was normal. In contrast, stabilization of beta-catenin in cholangiocyte precursors perturbed duct development and cholangiocyte differentiation. We conclude that beta-catenin is dispensable for biliary development but that its activity must be kept within tight limits. Our work is expected to significantly impact on in vitro differentiation of stem cells to cholangiocytes for toxicology studies and disease modeling. (C) 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.