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TISSUE-SPECIFIC STEM CELLS

Transcriptional Profiling of Bipotential Embryonic Liver Cells to Identify Liver Progenitor Cell Surface Markers

^aHuffington Center on Aging, Baylor College of Medicine, Houston, Texas, USA;
^bUnité de Génétique de la Différenciation, Institut Pasteur, Paris, France;
^cUnité des Cytokines et Développement Lymphoïde, Institut Pasteur, Paris, France

Key Words. Hepatic stem cells • Hepatocyte differentiation • Dicarbethoxydihydrocollidine • Cd24a • Notch1

Correspondence: Gretchen J. Darlington, Ph.D., Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. Telephone: 713-798-1565; Fax: 713-798-4161; e-mail: gretchen{at}bcm.tmc.edu

Received February 6, 2007; accepted for publication July 9, 2007.
First published online in STEM CELLS EXPRESS   July 19, 2007.



The ability to purify to homogeneity a population of hepatic progenitor cells from adult liver is critical for their characterization prior to any therapeutic application. As a step in this direction, we have used a bipotential liver cell line from 14 days postcoitum mouse embryonic liver to compile a list of cell surface markers expressed specifically by liver progenitor cells. These cells, known as bipotential mouse embryonic liver (BMEL) cells, proliferate in an undifferentiated state and are capable of differentiating into hepatocyte-like and cholangiocyte-like cells in vitro. Upon transplantation, BMEL cells are capable of differentiating into hepatocytes and cholangiocytes in vivo. Microarray and Gene Ontology (GO) analysis of gene expression in the 9A1 and 14B3 BMEL cell lines grown under proliferating and differentiating conditions was used to identify cell surface markers preferentially expressed in the bipotential undifferentiated state. This analysis revealed that proliferating BMEL cells express many genes involved in cell cycle regulation, whereas differentiation of BMEL cells by cell aggregation causes a switch in gene expression to functions characteristic of mature hepatocytes. In addition, microarray data and protein analysis indicated that the Notch signaling pathway could be involved in maintaining BMEL cells in an undifferentiated stem cell state. Using GO annotation, a list of cell surface markers preferentially expressed on undifferentiated BMEL cells was generated. One marker, Cd24a, is specifically expressed on progenitor oval cells in livers of diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate-treated animals. We therefore consider Cd24a expression a candidate molecule for purification of hepatic progenitor cells.

Disclosure of potential conflicts of interest is found at the end of this article.