title: The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts.
abstract: Hepatic stem/progenitor cells, hepatoblasts, have a high proliferative ability and can differentiate into mature hepatocytes and cholangiocytes. Therefore, these cells are considered to be useful for regenerative medicine and drug screening for liver diseases. However, it is problem that in vitro maturation of hepatoblasts is insufficient in the present culture system. In this study, a novel regulator to induce hepatic differentiation was identified and the molecular function of this factor was examined in embryonic day 13 hepatoblast culture with maturation factor, oncostatin M and extracellular matrices. Overexpression of the basic helix-loop-helix type transcription factor, Mist1, induced expression of mature hepatocytic markers such as carbamoyl-phosphate synthetase1 and several cytochrome P450 (CYP) genes in this culture system. In contrast, Mist1 suppressed expression of cholangiocytic markers such as Sox9, Sox17, Ck19, and Grhl2. CYP3A metabolic activity was significantly induced by Mist1 in this hepatoblast culture. In addition, Mist1 induced liver-enriched transcription factors, CCAAT/enhancer-binding protein α and Hepatocyte nuclear factor 1α, which are known to be involved in liver functions. These results suggest that Mist1 partially induces mature hepatocytic expression and function accompanied by the down-regulation of cholangiocytic markers.
authors.affiliation: Department of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Chikada
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-4 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-4 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Yanagida
authors.affiliation: Division of Stem Cell Therapy, Center for Stem Cell and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, 4-6-4 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.|Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305-5461, USA.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Nakauchi
authors.affiliation: Department of Molecular Life Sciences, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
authors.forename: Akihide
authors.initials: A
authors.lastname: Kamiya
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian; D005333:Fetus; D005786:Gene Expression Regulation; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053539:Keratin-19 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053683:Oncostatin M / Q000494:pharmacology; D061251:Primary Cell Culture; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D008565:Membrane Proteins
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D051538:Hepatocyte Nuclear Factor 1-alpha; D053539:Keratin-19; D053683:Oncostatin M; D055758:SOX9 Transcription Factor; D055760:SOXF Transcription Factors; D014157:Transcription Factors; C491312:Bhlha15 protein, mouse; C530718:CEBPA protein, mouse; C527933:Sox9 protein, mouse; C552738:grainy head-like 2 protein, mouse; C496508:Cyp3a11 protein, mouse; D008565:Membrane Proteins