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Hepatocytes express stem cell markers under the influence of growth factors in vitro and during transdifferentiation to billiary epithelial cells in vivo
Author(s) -
Bhave Vishakha Sudhir,
Bowen William C,
Paranjpe Shirish G,
Michalopoulos George K
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.363.4
Subject(s) - transdifferentiation , biology , stem cell , microbiology and biotechnology , stem cell marker , homeobox protein nanog , klf4 , liver regeneration , adult stem cell , sox2 , cellular differentiation , embryonic stem cell , cancer research , regeneration (biology) , induced pluripotent stem cell , biochemistry , gene
The objective of our present work was to test if hepatocytes express stem cell markers during regeneration or transdifferentiation. An in vitro model of primary rat hepatocytes and an in vivo model of transdifferentiation were used. Primary rat hepatocytes were cultured hepatocyte growth factor and epidermal growth factor. Plates were harvested at 0, 2, 4, 6, 8, and 10 days for mRNA, protein, and immunocytochemistry. The RE1‐silencing transcription factor that has previously been shown to regulate the expression of other stem cell markers was upregulated along with stem cell markers like Oct3/4, Nanog, cMyc, Klf4 in the presence of growth factors. Studies from our laboratory have shown that hepatocytes transdifferentiate to billiary epithelial (BE) cells in vivo in case of impaired billiary regeneration following bile duct ligation (BDL) and subsequent administration of billiary toxicant methylene dianiline (DAPM). We found that one week after BDL? treatment to rats, there was an upregulated expression of stem cell markers by hepatocytes. The levels reverted back by week 4. The fact that hepatocytes transiently express stem cell markers (responsible for maintaining pluripotency in embryonic stem cells) is interesting and could be a mechanism that facilitates their transdifferentiation to BE. This work is supported by 5R01CA103958‐05 titled HGF and signaling pathways in hepatic tissue assembly.