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First published online May 8, 2009
doi: 10.1242/10.1242/dev.031369

Development 136, 1951-1960 (2009)
Published by The Company of Biologists 2009
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Potential hepatic stem cells reside in EpCAM+ cells of normal and injured mouse liver

Mayuko Okabe1,*, Yuko Tsukahara1,*, Minoru Tanaka1,*,{dagger}, Kaori Suzuki1, Shigeru Saito1, Yoshiko Kamiya1, Tohru Tsujimura2, Koji Nakamura3 and Atsushi Miyajima1

1 Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
2 Department of Pathology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
3 LivTech, Miyamae-ku, Kawasaki, Kanagawa 216-0001, Japan.

{dagger} Author for correspondence (e-mail: tanaka{at}iam.u-tokyo.ac.jp)

Accepted 31 March 2009

Hepatic oval cells are considered to be facultative hepatic stem cells (HSCs) that differentiate into hepatocytes and cholangiocytes in severely injured liver. Hepatic oval cells have also been implicated in tumorigenesis. However, their nature and origin remain elusive. To isolate and characterize mouse oval cells, we searched for cell surface molecules expressed on oval cells and analyzed their nature at the single-cell level by flow cytometric analysis and in the in vitro colony formation assay. We demonstrate that epithelial cell adhesion molecule (EpCAM) is expressed in both mouse normal cholangiocytes and oval cells, whereas its related protein, TROP2, is expressed exclusively in oval cells, establishing TROP2 as a novel marker to distinguish oval cells from normal cholangiocytes. EpCAM+ cells isolated from injured liver proliferate to form colonies in vitro, and the clonally expanded cells differentiate into hepatocytes and cholangiocytes, suggesting that the oval cell fraction contains potential HSCs. Interestingly, such cells with HSC characteristics exist among EpCAM+ cells of normal liver. Intriguingly, comparison of the colony formation of EpCAM+ cells in normal and injured liver reveals little difference in the number of potential HSCs, strongly suggesting that most proliferating mouse oval cells represent transit-amplifying cells rather than HSCs.

Key words: Hepatic stem cell, Oval cell, EpCAM, TROP2 (TACSTD2), Hepatocyte, Cholangiocyte, Liver injury


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Development 2009 136: e1105. [Full Text]  





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