オカノ　テルオ   OKANO Teruo   岡野　光夫    所属   研究施設 研究施設    職種   特任顧問
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	CCAAT/enhancer binding protein-mediated regulation of TGFβ receptor 2 expression determines the hepatoblast fate decision.
掲載誌名	正式名：Development (Cambridge, England) 略　 称：Development ISSNコード：(1477-9129)0950-1991(Linking)
掲載区分	国外
巻・号・頁	141(1),pp.91-100
著者・共著者	Takayama Kazuo, Kawabata Kenji, Nagamoto Yasuhito, Inamura Mitsuru, Ohashi Kazuo, Okuno Hiroko, Yamaguchi Tomoko, Tashiro Katsuhisa, Sakurai Fuminori, Hayakawa Takao, Okano Teruo, Furue Miho Kusada, Mizuguchi Hiroyuki
発行年月	2014/01
概要	Human embryonic stem cells (hESCs) and their derivatives are expected to be used in drug discovery, regenerative medicine and the study of human embryogenesis. Because hepatocyte differentiation from hESCs has the potential to recapitulate human liver development in vivo, we employed this differentiation method to investigate the molecular mechanisms underlying human hepatocyte differentiation. A previous study has shown that a gradient of transforming growth factor beta (TGFβ) signaling is required to segregate hepatocyte and cholangiocyte lineages from hepatoblasts. Although CCAAT/enhancer binding proteins (c/EBPs) are known to be important transcription factors in liver development, the relationship between TGFβ signaling and c/EBP-mediated transcriptional regulation in the hepatoblast fate decision is not well known. To clarify this relationship, we examined whether c/EBPs could determine the hepatoblast fate decision via regulation of TGFβ receptor 2 (TGFBR2) expression in the hepatoblast-like cells differentiated from hESCs. We found that TGFBR2 promoter activity was negatively regulated by c/EBPα and positively regulated by c/EBPβ. Moreover, c/EBPα overexpression could promote hepatocyte differentiation by suppressing TGFBR2 expression, whereas c/EBPβ overexpression could promote cholangiocyte differentiation by enhancing TGFBR2 expression. Our findings demonstrated that c/EBPα and c/EBPβ determine the lineage commitment of hepatoblasts by negatively and positively regulating the expression of a common target gene, TGFBR2, respectively.
DOI	10.1242/dev.103168
PMID	24284203