Notenboom R G, de Boer P A, Moorman A F, Lamers W H
Department of Anatomy and Embryology, University of Amsterdam, The Netherlands.
Development. 1996 Jan;122(1):321-32. doi: 10.1242/dev.122.1.321.
We have studied the expression patterns of ammonia-metabolising enzymes and serum proteins in intrasplenically transplanted embryonic rat hepatocytes by in situ hybridisation and immunohistochemical analysis. The enzymic phenotype of individually settled hepatocytes was compared with that of hepatocytes being organised into a three-dimensional hepatic structure. Our results demonstrate that development towards the terminally differentiated state with zonal differences in enzyme content requires the incorporation of hepatocytes into lobular structures. Outside such an architectural context, phenotypic maturation becomes arrested and hepatocytes linger in the protodifferentiated state. These features identify the foetal period as a crucial time for normal liver development and show that the establishment of the terminally differentiated hepatocellular phenotype, beginning with the differentiation of hepatocytes from the embryonic foregut, is realised via a multistep process.
我们通过原位杂交和免疫组织化学分析，研究了脾内移植的胚胎大鼠肝细胞中氨代谢酶和血清蛋白的表达模式。将单个定居的肝细胞的酶表型与组织成三维肝结构的肝细胞的酶表型进行了比较。我们的结果表明，向具有酶含量区域差异的终末分化状态发展需要将肝细胞纳入小叶结构。在这种结构背景之外，表型成熟会停滞，肝细胞会停留在原分化状态。这些特征确定了胎儿期是正常肝脏发育的关键时期，并表明从胚胎前肠的肝细胞分化开始的终末分化肝细胞表型的建立是通过一个多步骤过程实现的。
