Differentiation of chemically induced liver progenitor cells to cholangiocytes: Investigation of the optimal conditions
Differentiation of chemically induced liver progenitor cells to cholangiocytes: Investigation of the optimal conditions
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DOI：
10.1016/j.jbiosc.2020.07.009
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发表时间：
2020-11-01
影响因子：
2.8
通讯作者：
Eguchi, Susumu
中科院分区：
文献类型：
--
作者：
Huang, Yu;Sakai, Yusuke;Eguchi, Susumu
化学诱导的肝祖细胞（CLiP）在体外由成熟肝细胞转化而来，具有向肝细胞和胆管细胞分化的双潜能。本研究旨在探讨大鼠CLiPs诱导胆管（BD）的最佳条件。采用两步诱导方案诱导胆管细胞分化。我们研究了传代数、预孵育时间、Matrigel和小鼠胚胎成纤维细胞（MEF）饲养细胞对胆管细胞诱导的影响。与稳定的CLiPs相比，早期的CLiPs诱导BD效果更好。在诱导前延长CLiPs的预孵化时间可以延缓BD的形成。Matrigel为细胞提供了形成三维（3D）结构的空间，但从诱导阶段开始长期使用Matrigel并不有利于CLiPs向胆管细胞的分化。MEF饲养细胞通过Jag/Notch通路影响BD的形成和功能，以及基因和蛋白的表达。在适当的条件下，clip是胆管细胞分化的良好细胞来源，可能为体外研究胆管病变提供关键载体。(C) 2020，生物技术学会，日本。版权所有。
Chemically induced liver progenitor (CLiP) cells, converted in vitro from mature hepatocytes, possess the bipotentiality to differentiate into both hepatocytes and cholangiocytes. Here, we aimed to investigate the optimal conditions for bile duct (BD) induction from rat CLiPs. A two-step induction protocol was used for the differentiation of cholangiocytes. We investigated the effects of passage number, preincubation times, Matrigel, and mouse embryonic fibroblast (MEF) feeder cells on the induction of cholangiocytes. Earlier passages of CLiPs were better for BD induction compared with stable CLiPs. Extending the preincubation time of CLiPs before induction delayed the formation of the BD. Matrigel provided cells with space to form three-dimensional (3D) structures, but the long-term use of Matrigel from the induction step did not benefit the differentiation of CLiPs to cholangiocytes. MEF feeder cells, through the Jag/Notch pathway, affected BD formation and function, as well as gene and protein expression. CLiPs were a good cell source for cholangiocyte differentiation under appropriate conditions and may offer a key vehicle for the study of cholangiopathies in vitro. (C) 2020, The Society for Biotechnology, Japan. All rights reserved.