RRC ID 43399
Author Maezawa K, Miyazato K, Matsunaga T, Momose Y, Imamura T, Johkura K, Sasaki K, Ohmori S.
Title Expression of cytochrome P450 and transcription factors during in vitro differentiation of mouse embryonic stem cells into hepatocytes.
Journal Drug Metab Pharmacokinet
Abstract Hepatocyte differentiation markers were expressed in the cells differentiated from mouse embryonic stem (ES) cells. In the differentiating ES cells, Cyp1a1 mRNA was highly expressed during the early to middle stage; Cyp2c29, Cyp2e1, Cyp3a11 and Cyp7a1 mRNAs were expressed only at the late stage; Cyp7b1 mRNA was expressed throughout all stages. Alpha-fetoprotein and albumin were co-expressed with Cyp3a and Cyp1a, respectively. Aryl hydrocarbon receptor, aryl hydrocarbon receptor nuclear translocator and glucocorticoid receptor mRNAs were detected in differentiating ES cells throughout the culture period. Pregnane X receptor mRNA was detected only in cells cultured for more than 24 days. The expression levels of Cyp2c29, Cyp3a11 and Cyp7a1 and G6p mRNAs were increased in embryoid bodies that were cultured with culture medium containing acid fibroblast growth factor, hepatocyte growth factor (HGF) and oncostatin M for 12 or 18 days, then the medium was replaced by that without HGF. These findings suggested that the expression levels of Cyp genes in hepatocytes differentiated from ES cells were markedly changed in individual enzymes during the course of differentiation, and that the duration of incubation with the addition of HGF affected the expression of Cyps and hepatocytes marker proteins.
Volume 23(3)
Pages 188-95
Published 2008-1-1
DOI 10.2133/dmpk.23.188
PII JST.JSTAGE/dmpk/23.188
PMID 18574323
MeSH Animals Cell Culture Techniques Cell Differentiation / drug effects Cell Differentiation / genetics Cell Differentiation / physiology* Cells, Cultured Culture Media Cytochrome P-450 Enzyme System / genetics* Embryonic Stem Cells* / cytology Embryonic Stem Cells* / drug effects Embryonic Stem Cells* / enzymology Embryonic Stem Cells* / metabolism Gene Expression / drug effects Hepatocyte Growth Factor / pharmacology Hepatocytes* / cytology Hepatocytes* / drug effects Hepatocytes* / enzymology Hepatocytes* / metabolism Mice RNA, Messenger / genetics Transcription Factors / genetics*
IF 2.772
Times Cited 9
WOS Category PHARMACOLOGY & PHARMACY
Resource
Human and Animal Cells