Gene expression pattern in hepatic stem/progenitor cells during rat fetal development using complementary DNA microarrays

Authors

  • Petko M. Petkov,

    1. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
    3. Jackson Laboratories, Bar Harbor, ME
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    • P.M.P. and J.Z. contributed equally to this work.

  • Jiri Zavadil,

    1. Biotechnology Center and Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Pathology, NYU School of Medicine, New York, NY
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    • P.M.P. and J.Z. contributed equally to this work.

  • David Goetz,

    1. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
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  • Tearina Chu,

    1. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
    3. Department of Molecular Biology and Biochemistry, Mount Sinai School of Medicine, New York, NY
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  • Robert Carver,

    1. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
    3. Enzo Biochemical, Farmington, NY
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  • Charles E. Rogler,

    1. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
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  • Erwin P. Bottinger,

    1. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
    2. Biotechnology Center and Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY
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  • David A. Shafritz,

    1. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
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  • Mariana D. Dabeva

    Corresponding author
    1. Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY
    2. Department of Medicine, Albert Einstein College of Medicine, Bronx, NY
    • Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461
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    • fax: 718-430-8975


Abstract

To identify new and differentially expressed genes in rat fetal liver epithelial stem/progenitor cells during their proliferation, lineage commitment, and differentiation, we used a high throughput method—mouse complementary DNA (cDNA) microarrays—for analysis of gene expression. The gene expression pattern of rat hepatic cells was studied during their differentiation in vivo: from embryonic day (ED) 13 until adulthood. The differentially regulated genes were grouped into two clusters: a cluster of up-regulated genes comprised of 281 clones and a cluster of down-regulated genes comprised of 230 members. The expression of the latter increased abruptly between ED 16 and ED 17. Many of the overexpressed genes from the first cluster fall into distinct, differentially expressed functional groups: genes related to development, morphogenesis, and differentiation; calcium- and phospholipid-binding proteins and signal transducers; and cell adhesion, migration, and matrix proteins. Several other functional groups of genes that are initially down-regulated, then increase during development, also emerged: genes related to inflammation, blood coagulation, detoxification, serum proteins, amino acids, lipids, and carbohydrate metabolism. Twenty-eight genes overexpressed in fetal liver that were not detected in adult liver are suggested as potential markers for identification of liver progenitor cells. In conclusion, our data show that the gene expression program of fetal hepatoblasts differs profoundly from that of adult hepatocytes and that it is regulated in a specific manner with a major switch at ED 16 to 17, marking a dramatic change in the gene expression program during the transition of fetal liver progenitor cells from an undifferentiated to a differentiated state. Supplementary material for this article can be found on the HEPATOLOGY website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2004;39:617–627.)

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