Hepatology International

, Volume 2, Issue 1, pp 50–62

Stage-specific regulation of adhesion molecule expression segregates epithelial stem/progenitor cells in fetal and adult human livers

Authors

  • Mari Inada
    • Departments of Medicine and Pathology, Marion Bessin Liver Research CenterAlbert Einstein College of Medicine
    • Department of Medicine and Clinical Oncology, Graduate School of MedicineChiba University
  • Daniel Benten
    • Departments of Medicine and Pathology, Marion Bessin Liver Research CenterAlbert Einstein College of Medicine
  • Kang Cheng
    • Departments of Medicine and Pathology, Marion Bessin Liver Research CenterAlbert Einstein College of Medicine
  • Brigid Joseph
    • Departments of Medicine and Pathology, Marion Bessin Liver Research CenterAlbert Einstein College of Medicine
  • Ekaterine Berishvili
    • Departments of Medicine and Pathology, Marion Bessin Liver Research CenterAlbert Einstein College of Medicine
  • Sunil Badve
    • Department of PathologyIndiana University School of Medicine
  • Lennart Logdberg
    • Department of Pathology and Laboratory MedicineEmory University School of Medicine
  • Mariana Dabeva
    • Departments of Medicine and Pathology, Marion Bessin Liver Research CenterAlbert Einstein College of Medicine
    • Departments of Medicine and Pathology, Marion Bessin Liver Research CenterAlbert Einstein College of Medicine
Original Research

DOI: 10.1007/s12072-007-9023-4

Cite this article as:
Inada, M., Benten, D., Cheng, K. et al. Hepatol Int (2008) 2: 50. doi:10.1007/s12072-007-9023-4

Abstract

Purpose

Regulated expression of cell adhesion molecules could be critical in the proliferation, sequestration, and maintenance of stem/progenitor cells. Therefore, we determined fetal and adult stage-specific roles of cell adhesion in liver cell compartments.

Methods

We performed immunostaining for the adhesion molecules, E-cadherin and Ep-CAM, associated proteins, β-catenin and α-actinin, hepatobiliary markers, albumin, α-fetoprotein, and cytokeratin-19, and the proliferation marker, Ki-67. Expression of albumin was verified by in situ mRNA hybridization.

Results

In the fetal liver, hepatoblasts showed extensive proliferation with wide expression of E-cadherin, β-catenin, and α-actinin, although Ep-CAM was expressed in these cells less intensely and focally in the cell membrane to indicate weak cell adhesion. Hepatoblasts in ductal plate and bile ducts showed less proliferation and Ep-CAM was intensely expressed in these cells throughout the cell membrane, indicating strong adhesion. In some ductal plate cells, β-catenin was additionally in the cytoplasm and nucleus, suggesting active cell signaling by adhesion molecules. In adult livers, cells were no longer proliferating and E-cadherin, β-catenin, and α-actinin were expressed in hepatocytes throughout, whereas Ep-CAM was expressed in only bile duct cells. Some cells in ductal structures of the adult liver with Ep-CAM coexpressed albumin and cytokeratin-19, indicating persistence of fetal-like stem/progenitor cells.

Conclusions

Regulated expression of Ep-CAM supported proliferation in fetal hepatoblasts through weak adhesion and helped in biliary morphogenesis by promoting stronger adhesion in hepatoblasts during this process. Restriction of Ep-CAM expression to bile ducts in the adult liver presumably facilitated sequestration of stem/progenitor cells. This stage-specific and cell compartment-related regulation of adhesion molecules should be relevant for defining how liver stem/progenitor cells enter, exit, and remain in hepatic niches during both health and disease.

Keywords

Adhesion moleculesCell proliferationStem cells

Copyright information

© Asian Pacific Association for the Study of the Liver 2007