van Roon M A, Aten J A, van Oven C H, Charles R, Lamers W H
Department of Anatomy and Embryology, University of Amsterdam.
Dev Biol. 1989 Dec;136(2):508-16. doi: 10.1016/0012-1606(89)90276-5.
To gain insight into the mechanisms that govern the first steps of liver-specific enzyme accumulation upon hormone exposure, the initial accumulation of carbamoylphosphate synthetase, phosphoenolpyruvate carboxykinase, and arginase in monolayer cultures of Embryonic Day 14 rat hepatocytes was studied. By using different fluorescent labels the initial accumulation of two enzymes could be studied simultaneously in individual cells. Both microscopic and flow cytometric analyses showed that the initial expression of genes that are under the same hormonal control appears to lack the coordinated regulation of expression that is seen later in development. The coordination is gradually established during exposure to hormones. Once gene expression becomes coordinated, the enzyme content appears to increase continuously with time. Therefore, we postulate that within individual embryonic hepatocytes the initial intercellular heterogeneity in rate of accumulation of a particular protein may be the result of competition of different genes for an initially limiting supply of common regulatory factors, leading to random differences in the rate of accumulation of the respective gene products. This makes the initiation of liver-specific gene expression within the hepatocytes a stochastic event.
为深入了解激素暴露后肝脏特异性酶积累初期的调控机制，我们研究了胚胎第14天大鼠肝细胞单层培养物中氨甲酰磷酸合成酶、磷酸烯醇式丙酮酸羧激酶和精氨酸酶的初始积累情况。通过使用不同的荧光标记，可以在单个细胞中同时研究两种酶的初始积累。显微镜和流式细胞术分析均表明，受相同激素控制的基因的初始表达似乎缺乏发育后期所见的协调表达调控。在激素暴露过程中，这种协调性会逐渐建立。一旦基因表达变得协调，酶含量似乎会随时间持续增加。因此，我们推测，在单个胚胎肝细胞内，特定蛋白质积累速率的初始细胞间异质性可能是不同基因竞争共同调控因子的初始有限供应的结果，导致各自基因产物积累速率出现随机差异。这使得肝细胞内肝脏特异性基因表达的起始成为一个随机事件。
