Kennedy S, Rettinger S, Flye M W, Ponder K P
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Hepatology. 1995 Jul;22(1):160-8.
One hypothesis is that postnatal liver growth involves replication of mature hepatocytes, which have an unlimited proliferative potential. An alternative viewpoint is that only certain periportal cells can replicate extensively and that daughter cells stream slowly from the periportal to the pericentral region of the liver. Transgenic mice expressing the beta-galactosidase (beta-gal) gene from the human alpha 1 antitrypsin promoter were used to examine the proliferative potential of hepatocytes. Surprisingly, only 10% of hepatocytes in two different transgenic lines stain blue with X-gal. In neonatal animals, singlets or doublets of expressing cells are randomly scattered throughout the liver. Although the overall frequency of blue cells is similar in older animals, these cells are present in much larger clusters, suggesting that individual expressing cells have replicated to form a clonally derived cluster. Expression patterns are not altered by the administration of an acute phase stimulus or by the performance a partial hepatectomy, suggesting that the expression state cannot be easily altered, and making it more likely that the expression state is indeed fixed. These results suggest that the clusters of blue cells are clonally derived in the transgenic mice. They argue that the parenchymal hepatocyte is responsible for growth in the postnatal liver and that streaming of liver cells does not occur.
一种假说认为，出生后肝脏的生长涉及成熟肝细胞的复制，而成熟肝细胞具有无限的增殖潜能。另一种观点则认为，只有某些门周细胞能够大量复制，并且子细胞从肝脏的门周区域缓慢流向中央静脉周围区域。利用从人α1抗胰蛋白酶启动子表达β-半乳糖苷酶（β-gal）基因的转基因小鼠来检测肝细胞的增殖潜能。令人惊讶的是，在两个不同的转基因品系中，只有10%的肝细胞用X-gal染色呈蓝色。在新生动物中，表达细胞的单倍体或双倍体随机散布于整个肝脏。虽然在年龄较大的动物中蓝色细胞的总体频率相似，但这些细胞以大得多的簇状形式存在，这表明单个表达细胞已经复制形成了一个克隆衍生的簇。给予急性期刺激或进行部分肝切除术后，表达模式并未改变，这表明表达状态不易改变，并且更有可能表达状态确实是固定的。这些结果表明，转基因小鼠中蓝色细胞簇是克隆衍生的。他们认为实质肝细胞是出生后肝脏生长的原因，并且肝细胞不会发生流动。
