Molecular basis of transdifferentiation of pancreas to liver
Molecular basis of transdifferentiation of pancreas to liver
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DOI：
10.1038/35046522
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发表时间：
2000-12-01
影响因子：
21.3
通讯作者：
Tosh, D
中科院分区：
文献类型：
--
作者：
Shen, CN;Slack, JMW;Tosh, D
在动物实验和人类病理学中已经描述了胰腺中肝灶的外观。在这里，我们表明，胰腺细胞可以转化为肝细胞的治疗与合成糖皮质激素，地塞米松。这发生在胰腺细胞系AR 42 J-B13和小鼠胚胎胰腺芽的器官培养物中。我们已经建立了这种转分化背后的机制的几个特征。我们表明，肝细胞的比例直接来自分化的外分泌样细胞，没有干预细胞分裂。这种转化与转录因子C/EBP β的诱导和分化的肝脏产物的活化有关。将C/EBP β转染到细胞中可以引起转分化;相反，C/EBP β的显性阴性形式可以抑制该过程。这些结果表明，C/EBP β是区分肝脏和胰腺分化程序的关键组分。
The appearance of hepatic foci in the pancreas has been described in animal experiments and in human pathology. Here we show that pancreatic cells can be converted into hepatocytes by treatment with a synthetic glucocorticoid, dexamethasone. This occurs both in a pancreatic cell line, AR42J-B13, and in organ cultures of pancreatic buds from mouse embryos. We have established several features of the mechanism behind this transdifferentiation. We show that a proportion of the hepatocytes arises directly from differentiated exocrine-like cells, with no intervening cell division. This conversion is associated with induction of the transcription factor C/EBP beta and the activation of differentiated hepatic products. Transfection of C/EBP beta into the cells can provoke transdifferentiation; conversely, a dominant-negative form of C/EBP beta can inhibit the process. These results indicate that C/EBP beta is a key component that distinguishes the liver and pancreatic programmes of differentiation.