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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans.
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Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans.

机译：上皮细胞粘附分子（EpCAM）标记人干细胞/祖细胞新衍生的肝细胞。

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摘要

Epithelial cell adhesion molecule (EpCAM) is a surface marker on human hepatic stem/progenitor cells that is reported as absent on mature hepatocytes. However, it has also been noted that in cirrhotic livers of diverse causes, many hepatocytes have EpCAM surface expression; this may represent aberrant EpCAM expression in injured hepatocytes or, as we now hypothesize, persistence of EpCAM in hepatocytes that have recently derived from hepatobiliary progenitors. To evaluate this concept, we investigated patterns of EpCAM expression in hepatobiliary cell compartments of liver biopsy specimens from patients with all stages of chronic hepatitis B and C, studying proliferation, senescence and telomere lengths. We found that EpCAM(+) hepatocytes were rare in early stages of disease, became increasingly prominent in later stages in parallel with the emergence of ductular reactions, and were consistently arrayed around the periphery of cords of keratin 19(+) hepatobiliary cells of the ductular reaction, with which they shared EpCAM expression. Proliferating cell nuclear antigen (proliferation marker) and p21 (senescence marker) were both higher in hepatocytes in cirrhosis than in normal livers, but ductular reaction hepatobiliary cells had the highest proliferation rate, in keeping with being stem/progenitor cell-derived transit amplifying cells. Telomere lengths in EpCAM(+) hepatocytes in cirrhosis were higher than EpCAM(-) hepatocytes (P < 0.046), and relatively shorter than those in the corresponding ductular reaction hepatobiliary cells (P = 0.057). CONCLUSION: These morphologic, topographic, immunophenotypic, and molecular data support the concept that EpCAM(+) hepatocytes in chronic viral hepatitis are recent progeny of the hepatobiliary stem/progenitor cell compartment through intermediates of the transit amplifying, ductular reaction hepatobiliary cells.
机译：上皮细胞粘附分子（EpCAM）是人肝干/祖细胞上的表面标记，据报道在成熟肝细胞上不存在。然而，也已经注意到，在各种原因的肝硬化肝中，许多肝细胞具有EpCAM表面表达。这可能代表受损的肝细胞中EpCAM的异常表达，或者如我们现在所假设的那样，这表明EpCAM在最近源自肝胆祖细胞的肝细胞中持续存在。为了评估这一概念，我们研究了慢性乙型和丙型肝炎所有阶段患者肝活检标本的肝胆细胞隔室中EpCAM的表达模式，研究了增殖，衰老和端粒长度。我们发现，EpCAM（+）肝细胞在疾病的早期阶段是罕见的，在后期随着导管反应的出现而变得越来越突出，并且始终围绕着角蛋白19（+）肝胆管的脐带周围排列。导管反应，与他们共享EpCAM表达。肝硬化的肝细胞中增殖细胞核抗原（增殖标志物）和p21（衰老标志物）均高于正常肝脏，但导管反应性肝胆细胞具有最高的增殖率，与干细胞/祖细胞衍生的转运扩增细胞一致。肝硬化中EpCAM（+）肝细胞的端粒长度高于EpCAM（-）肝细胞（P <0.046），且相对短于相应的导管反应性肝胆细胞（P = 0.057）。结论：这些形态，地形，免疫表型和分子数据支持这一概念，即慢性病毒性肝炎中的EpCAM（+）肝细胞是肝胆干/祖细胞隔室的新近子代，是通过转运放大，导管反应性肝胆细胞的中间产物。

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