Hepatic specification of the gut endoderm in vitro: Cell signaling and transcriptional control
Hepatic specification of the gut endoderm in vitro: Cell signaling and transcriptional control
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DOI：
10.1101/gad.10.13.1670
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发表时间：
1996-07-01
影响因子：
10.5
通讯作者：
Zaret, KS
中科院分区：
文献类型：
--
作者：
Gualdi, R;Bossard, P;Zaret, KS
我们已经研究了多能性肠内胚层肝细胞的初步发展，使用组织外植体系统从小鼠胚胎。我们不仅发现了指定肝分化的细胞相互作用，而且还发现了那些在通常产生其他组织的内胚层区域中阻断肝发生的细胞相互作用。结果暗示了早期肝脏特化中的阳性和阴性信号。前体肠内胚层中白蛋白增强子的体内足迹显示，转录沉默但潜在活性的染色质的特征在于HNF-3位点的占据。在肝脏特化后，随着基因变得活跃，许多其他因子结合附近的位点。因此，多能细胞中的基因可以通过染色质中的进入点标记为潜在表达，在细胞类型特化期间，额外的因子结合在染色质中。这些发现也为不同内胚层细胞类型的进化起源提供了深入了解。
We have studied the initial development of pluripotent gut endoderm to hepatocytes using a tissue explant system from mouse embryos. We not only find cellular interactions that specify hepatic differentiation but also those that block hepatogenesis in regions of the endoderm that normally give rise to other tissues. The results Implicate both positive and negative signaling in early hepatic specification. In vivo footprinting of the albumin enhancer in precursor gut endoderm shows that the transcriptionally silent but potentially active chromatin is characterized by occupancy of an HNF-3 site. Upon hepatic specification, a host of other factors bind nearby sites as the gene becomes active. Genes in pluripotent cells therefore may be marked for potential expression by entry points in chromatin, where additional factors bind during cell type specification. The findings also provide insight into the evolutionary origin of different endodermal cell types.