Recapitulation of in vivo gene expression during hepatic differentiation from murine embryonic stem cells.
Hepatic differentiation at the molecular level is poorly understood, mainly because of the lack of a suitable model. Recently, using adherent monoculture conditions, we demonstrated the direct differentiation of hepatocytes from embryonic stem (ES) cells. In this study, we exploited the direct differentiation model to compare the gene expression profiles of ES cell-derived hepatocytes with adult mouse liver using DNA microarray technology. The results showed that the ES cell-derived hepatocyte gene expression pattern is very similar to adult mouse liver. Through further analysis of gene ontology categories for the 232 most radically altered genes, we found that the significant categories related to hepatic function. Furthermore, through the use of small interfering RNA technology in vitro, hepatocyte nuclear factor 3beta/FoxA2 was identified as having an essential role in hepatic differentiation. These results demonstrate that ES cell-derived hepatocytes recapitulate the gene expression profile of adult mouse liver to a significant degree and indicate that our direct induction system progresses via endoderm differentiation. In conclusion, our system closely mimics in vivo hepatic differentiation at the transcriptional level and could, therefore, be useful for studying the molecular basis of hepatocyte differentiation per se.
Yamamoto
Yusuke
Y
Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo, Japan.
Teratani
Takumi
T
Yamamoto
Hanako
H
Quinn
Gary
G
Murata
Sigenori
S
Ikeda
Rieko
R
Kinoshita
Kenji
K
Matsubara
Kenichi
K
Kato
Takashi
T
Ochiya
Takahiro
T
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004798:Enzymes / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology* / Q000502:physiology*; D008099:Liver / Q000166:cytology / Q000196:embryology*; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011506:Proteins / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014162:Transfection
D004798:Enzymes; D011506:Proteins; D034741:RNA, Small Interfering; D012313:RNA