Gualdi R, Bossard P, Zheng M, Hamada Y, Coleman J R, Zaret K S
Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
Genes Dev. 1996 Jul 1;10(13):1670-82. doi: 10.1101/gad.10.13.1670.
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.
我们利用小鼠胚胎的组织外植体系统研究了多能性肠内胚层向肝细胞的初始发育过程。我们不仅发现了决定肝分化的细胞间相互作用，还发现了在内胚层中通常会产生其他组织的区域中阻止肝发生的细胞间相互作用。这些结果表明，在早期肝特化过程中存在正负信号传导。对前体肠内胚层中白蛋白增强子的体内足迹分析表明，转录沉默但具有潜在活性的染色质的特征是HNF-3位点的占据。在肝特化过程中，随着基因变得活跃，许多其他因子会结合到附近的位点。因此，多能细胞中的基因可能通过染色质中的进入点被标记为潜在表达，在细胞类型特化过程中，其他因子会结合到这些进入点。这些发现还为不同内胚层细胞类型的进化起源提供了见解。
