Open AccessTranscriptional Profiling of Bipotential Embryonic Liver Cells to Identify Liver Progenitor Cell Surface Markers
Author(s) -
Ochsner Scott A.,
StrickMarchand Hélène,
Qiu Qiong,
Venable Susan,
Dean Adam,
Wilde Margaret,
Weiss Mary C.,
Darlington Gretchen J.
Publication year - 2007
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2007-0101
Subject(s) - biology , progenitor cell , embryonic stem cell , microbiology and biotechnology , stem cell , cellular differentiation , hepatocyte , stem cell marker , cell , gene expression profiling , cell culture , liver cytology , adult stem cell , cholangiocyte , gene expression , gene , in vitro , genetics , biochemistry , liver metabolism , endocrinology
Abstract 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.