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Zonal hierarchy of differentiation markers and nestin expression during oval cell mediated rat liver regeneration

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Abstract

Oval cells constitute a heterogeneous population of proliferating progenitors found in rat livers following carcinogenic treatment (2-acetylaminofluorene and 70% hepatectomy). The aim of this study was to investigate the cellular pattern of various differentiation and cell type markers in this model of liver regeneration. Immunophenotypic characterisation revealed at least two subtypes emerging from the portal field. First, a population of oval cells formed duct-like structures and expressed bile duct (CD49f) as well as hepatocytic markers (α-foetoprotein, CD26). Second, a population of non-ductular oval cells was detected between and distally from the ductules expressing the neural marker nestin and the haematopoietic marker Thy1. Following oval cell isolation, a subset of the nestin-positive cells was shown to co-express hepatocytic and epithelial markers (albumin, CD26, pancytokeratin) and could be clearly distinguished from anti-desmin reactive hepatic stellate cells. The gene expression profiles (RT-PCR) of isolated oval cells and oval cell liver tissue were found to be similar to foetal liver (ED14). The present results suggest that the two oval cell populations are organised in a zonal hierarchy with a marker gradient from the inner (displaying hepatocytic and biliary markers) to the outer zone (showing hepatocytic and extrahepatic progenitor markers) of the proliferating progeny clusters.

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Acknowledgments

The authors would like to thank Sabine Wilde and Sabrina Goldmann for their excellent work in preparing the immunolabelling figures for this article. We would furthermore like to express our appreciation to Andrew Entwistle for his critical review of this manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (DFG) (grant KO 2218/1-2) and by a grant within the Research Promotion Programme 2002 of the Faculty of Medicine and University Hospital of the Georg-August University Goettingen.

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  1. Department of General Surgery, University Hospital, Robert-Koch-Strasse 40, 37099, Goettingen, Germany

    Sarah Koenig, Heinz Becker & Petra Krause

  2. Department of Biochemistry I, Centre of Biochemistry and Molecular Cell Biology, Georg-August University Goettingen, Humboldtallee 23, 37075, Goettingen, Germany

    Irmelin Probst

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  1. Sarah Koenig
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Correspondence to Sarah Koenig.

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Koenig, S., Probst, I., Becker, H. et al. Zonal hierarchy of differentiation markers and nestin expression during oval cell mediated rat liver regeneration. Histochem Cell Biol 126, 723–734 (2006). https://doi.org/10.1007/s00418-006-0204-3

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