title: Direct hepatic fate specification from mouse embryonic stem cells.
abstract: The molecules responsible for hepatic differentiation from embryonic stem (ES) cells have yet to be elucidated. Here we have identified growth factors that allow direct hepatic fate-specification from ES cells by using simple adherent monolayer culture conditions. ES cell-derived hepatocytes showed liver-specific characteristics, including several metabolic activities, suggesting that ES cells can differentiate into functional hepatocytes without the requirement for embryoid body (EB) formation, in vivo transplantation, or a coculture system. Most importantly, transplantation of ES cell-derived hepatocytes in mice with cirrhosis showed significant therapeutic effects. In conclusion, this novel system for hepatic fate specification will help elucidate the precise molecular mechanisms of hepatic differentiation in vitro and could represent an attractive approach for developing stem cell therapies for treatment of hepatic disease in humans. Supplementary material for this article can be found on the HEPATOLOGY website ( http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).
authors.affiliation: Section for Studies on Metastasis, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Teratani
authors.forename: Hanako
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Aoyagi
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Akira
authors.initials: A
authors.lastname: Asari
authors.forename: Gary
authors.initials: G
authors.lastname: Quinn
authors.forename: Hideo
authors.initials: H
authors.lastname: Sasaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Terada
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006133:Growth Substances / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D051379:Mice; D008815:Mice, Inbred Strains; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D006133:Growth Substances; D049452:Green Fluorescent Proteins