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Published 7 January 2002. doi:10.1083/jcb.200108066
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© The Rockefeller University Press, 0021-9525/2002/1/173 $5.00
The Journal of Cell Biology, Volume 156, Number 1, January 7, 2002 173-184

Article

Clonal identification and characterization of self-renewing pluripotent stem cells in the developing liver



Atsushi Suzuki1, Yun-wen Zheng1, Shin Kaneko2, Masafumi Onodera2, Katashi Fukao1, Hiromitsu Nakauchi2,3 and Hideki Taniguchi1

1 Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan
2 Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, and CREST (Japan Science and Technology Corporation), Tsukuba, Ibaraki 305-8575, Japan
3 Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan

Address correspondence to Hiromitsu Nakauchi, Dept. of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. Tel.: 81-298-53-3462. Fax: 81-298-53-6966. E-mail: nakauchi{at}md.tsukuba.ac.jp

Using flow cytometry and single cell–based assays, we prospectively identified hepatic stem cells with multilineage differentiation potential and self-renewing capability. These cells could be clonally propagated in culture where they continuously produced hepatocytes and cholangiocytes as descendants while maintaining primitive stem cells. When cells that expanded in vitro were transplanted into recipient animals, they morphologically and functionally differentiated into hepatocytes and cholangiocytes with reconstitution of hepatocyte and bile duct structures. Furthermore, these cells differentiated into pancreatic ductal and acinar cells or intestinal epithelial cells when transplanted into pancreas or duodenal wall. These data indicate that self-renewing pluripotent stem cells persist in the developing mouse liver and that such cells can be induced to become cells of other organs of endodermal origin under appropriate microenvironment. Manipulation of hepatic stem cells may provide new insight into therapies for diseases of the digestive system.

Key Words: liver; hepatocyte; stem cell; self-renew; endoderm


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