Expression of cytochrome P450 and transcription factors during in vitro differentiation of mouse embryonic stem cells into hepatocytes.
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.
Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
Kayoko
K
Maezawa
Kenji
K
Miyazato
Tamihide
T
Matsunaga
Yasuyuki
Y
Momose
Tetsuya
T
Imamura
Kohei
K
Johkura
Katsunori
K
Sasaki
Shigeru
S
Ohmori
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D003470:Culture Media; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D003470:Culture Media; D012333:RNA, Messenger; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor; D003577:Cytochrome P-450 Enzyme System