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The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts

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 ma...

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Autores principales: Chikada, Hiromi, Ito, Keiichi, Yanagida, Ayaka, Nakauchi, Hiromitsu, Kamiya, Akihide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601036/
https://www.ncbi.nlm.nih.gov/pubmed/26456005
http://dx.doi.org/10.1038/srep14989
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author Chikada, Hiromi
Ito, Keiichi
Yanagida, Ayaka
Nakauchi, Hiromitsu
Kamiya, Akihide
author_facet Chikada, Hiromi
Ito, Keiichi
Yanagida, Ayaka
Nakauchi, Hiromitsu
Kamiya, Akihide
author_sort Chikada, Hiromi
collection PubMed
description 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.
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spelling pubmed-46010362015-10-21 The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts Chikada, Hiromi Ito, Keiichi Yanagida, Ayaka Nakauchi, Hiromitsu Kamiya, Akihide Sci Rep Article 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. Nature Publishing Group 2015-10-12 /pmc/articles/PMC4601036/ /pubmed/26456005 http://dx.doi.org/10.1038/srep14989 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chikada, Hiromi
Ito, Keiichi
Yanagida, Ayaka
Nakauchi, Hiromitsu
Kamiya, Akihide
The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts
title The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts
title_full The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts
title_fullStr The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts
title_full_unstemmed The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts
title_short The basic helix-loop-helix transcription factor, Mist1, induces maturation of mouse fetal hepatoblasts
title_sort basic helix-loop-helix transcription factor, mist1, induces maturation of mouse fetal hepatoblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601036/
https://www.ncbi.nlm.nih.gov/pubmed/26456005
http://dx.doi.org/10.1038/srep14989
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