Origin of pancreatic endocrine cells from biliary duct epithelium

Origin of pancreatic endocrine cells from biliary duct epithelium
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DOI:
10.1007/s00018-008-8427-1
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发表时间:
2008-11-01
影响因子:
8
通讯作者:
Slack, J. M. W.
Slack, J. M. W.
中科院分区:
生物学1区
文献类型:
--
作者:
Eberhard, D.;Tosh, D.;Slack, J. M. W.

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我们描述了一个外植体培养系统,研究胰腺型内分泌细胞的形成由胆道。在该模型中,β细胞和其他内分泌细胞出现在胆管上皮中,并且它们的数量增加。起源于导管上皮的证据有三方面。首先,分化细胞瞬时共表达胰岛素并结合扁豆凝集素。其次,从Alb-Cre-R26 R-LacZ小鼠分离的培养物中的β-细胞是β-半乳糖苷酶阳性的。第三,胆管上皮和ROSA 26胰腺芽的共培养显示内分泌细胞不从胰腺迁移。胰腺转录因子Pdx 1、HNF 6和Sox 9的表达是广泛的,抑制内分泌发育的Hes 1也是如此,而前内分泌转录因子Ngn 3的表达是短暂的,与内分泌细胞分化的早期阶段一致。烟酰胺会增加形成的β细胞数量,而EGF+LIF完全抑制它们的形成。
We describe an explant culture system to study the formation of pancreatic-type endocrine cells by the biliary tract. In this model, beta-cells and other endocrine cells appear in the biliary duct epithelium and their number increases. Evidence for an origin from the duct epithelium is threefold. Firstly, differentiating cells transiently co-express insulin and bind Dolichos lectin. Secondly, beta-cells in cultures isolated from Alb-Cre-R26R-LacZ mice are beta-galactosidase positive. Thirdly, co-culture of biliary epithelium and ROSA26 pancreatic buds shows that endocrine cells do not migrate from the pancreas. The expression of the pancreatic transcription factors Pdx1, HNF6 and Sox9 is widespread, as is Hes1, which represses endocrine development, while that of Ngn3, which is a proendocrine transcription factor, is transient, consistent with an early stage of endocrine cell differentiation. Nicotinamide will increase the number of beta-cells formed, while EGF+LIF completely inhibits their formation.