TY - JOUR
T1 - Stage-specific regulation of adhesion molecule expression segregates epithelial stem/progenitor cells in fetal and adult human livers
AU - Inada, Mari
AU - Benten, Daniel
AU - Cheng, Kang
AU - Joseph, Brigid
AU - Berishvili, Ekaterine
AU - Badve, Sunil
AU - Logdberg, Lennart
AU - Dabeva, Mariana
AU - Gupta, Sanjeev
N1 - Funding Information:
Acknowledgments This study was supported in part by NIH grants R01 DK46952, P01 DK52956, and P20 GM075037
PY - 2008/3
Y1 - 2008/3
N2 - 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.
AB - 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.
KW - Adhesion molecules
KW - Cell proliferation
KW - Stem cells
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U2 - 10.1007/s12072-007-9023-4
DO - 10.1007/s12072-007-9023-4
M3 - Article
C2 - 19669279
AN - SCOPUS:69749103658
SN - 1936-0533
VL - 2
SP - 50
EP - 62
JO - Hepatology International
JF - Hepatology International
IS - 1
ER -