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Histone Deacetylase Inhibitor Valproic Acid Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells

In this study, we aimed to elucidate the effects and mechanism of action of valproic acid on hepatic differentiation from human induced pluripotent stem cell-derived hepatic progenitor cells. Human induced pluripotent stem cells were differentiated into endodermal cells in the presence of activin A...

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Autores principales: Kondo, Yuki, Iwao, Takahiro, Yoshihashi, Sachimi, Mimori, Kayo, Ogihara, Ruri, Nagata, Kiyoshi, Kurose, Kouichi, Saito, Masayoshi, Niwa, Takuro, Suzuki, Takayoshi, Miyata, Naoki, Ohmori, Shigeru, Nakamura, Katsunori, Matsunaga, Tamihide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119015/
https://www.ncbi.nlm.nih.gov/pubmed/25084468
http://dx.doi.org/10.1371/journal.pone.0104010
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author Kondo, Yuki
Iwao, Takahiro
Yoshihashi, Sachimi
Mimori, Kayo
Ogihara, Ruri
Nagata, Kiyoshi
Kurose, Kouichi
Saito, Masayoshi
Niwa, Takuro
Suzuki, Takayoshi
Miyata, Naoki
Ohmori, Shigeru
Nakamura, Katsunori
Matsunaga, Tamihide
author_facet Kondo, Yuki
Iwao, Takahiro
Yoshihashi, Sachimi
Mimori, Kayo
Ogihara, Ruri
Nagata, Kiyoshi
Kurose, Kouichi
Saito, Masayoshi
Niwa, Takuro
Suzuki, Takayoshi
Miyata, Naoki
Ohmori, Shigeru
Nakamura, Katsunori
Matsunaga, Tamihide
author_sort Kondo, Yuki
collection PubMed
description In this study, we aimed to elucidate the effects and mechanism of action of valproic acid on hepatic differentiation from human induced pluripotent stem cell-derived hepatic progenitor cells. Human induced pluripotent stem cells were differentiated into endodermal cells in the presence of activin A and then into hepatic progenitor cells using dimethyl sulfoxide. Hepatic progenitor cells were matured in the presence of hepatocyte growth factor, oncostatin M, and dexamethasone with valproic acid that was added during the maturation process. After 25 days of differentiation, cells expressed hepatic marker genes and drug-metabolizing enzymes and exhibited drug-metabolizing enzyme activities. These expression levels and activities were increased by treatment with valproic acid, the timing and duration of which were important parameters to promote differentiation from human induced pluripotent stem cell-derived hepatic progenitor cells into hepatocytes. Valproic acid inhibited histone deacetylase activity during differentiation of human induced pluripotent stem cells, and other histone deacetylase inhibitors also enhanced differentiation into hepatocytes. In conclusion, histone deacetylase inhibitors such as valproic acid can be used to promote hepatic differentiation from human induced pluripotent stem cell-derived hepatic progenitor cells.
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spelling pubmed-41190152014-08-04 Histone Deacetylase Inhibitor Valproic Acid Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells Kondo, Yuki Iwao, Takahiro Yoshihashi, Sachimi Mimori, Kayo Ogihara, Ruri Nagata, Kiyoshi Kurose, Kouichi Saito, Masayoshi Niwa, Takuro Suzuki, Takayoshi Miyata, Naoki Ohmori, Shigeru Nakamura, Katsunori Matsunaga, Tamihide PLoS One Research Article In this study, we aimed to elucidate the effects and mechanism of action of valproic acid on hepatic differentiation from human induced pluripotent stem cell-derived hepatic progenitor cells. Human induced pluripotent stem cells were differentiated into endodermal cells in the presence of activin A and then into hepatic progenitor cells using dimethyl sulfoxide. Hepatic progenitor cells were matured in the presence of hepatocyte growth factor, oncostatin M, and dexamethasone with valproic acid that was added during the maturation process. After 25 days of differentiation, cells expressed hepatic marker genes and drug-metabolizing enzymes and exhibited drug-metabolizing enzyme activities. These expression levels and activities were increased by treatment with valproic acid, the timing and duration of which were important parameters to promote differentiation from human induced pluripotent stem cell-derived hepatic progenitor cells into hepatocytes. Valproic acid inhibited histone deacetylase activity during differentiation of human induced pluripotent stem cells, and other histone deacetylase inhibitors also enhanced differentiation into hepatocytes. In conclusion, histone deacetylase inhibitors such as valproic acid can be used to promote hepatic differentiation from human induced pluripotent stem cell-derived hepatic progenitor cells. Public Library of Science 2014-08-01 /pmc/articles/PMC4119015/ /pubmed/25084468 http://dx.doi.org/10.1371/journal.pone.0104010 Text en © 2014 Kondo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kondo, Yuki
Iwao, Takahiro
Yoshihashi, Sachimi
Mimori, Kayo
Ogihara, Ruri
Nagata, Kiyoshi
Kurose, Kouichi
Saito, Masayoshi
Niwa, Takuro
Suzuki, Takayoshi
Miyata, Naoki
Ohmori, Shigeru
Nakamura, Katsunori
Matsunaga, Tamihide
Histone Deacetylase Inhibitor Valproic Acid Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells
title Histone Deacetylase Inhibitor Valproic Acid Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells
title_full Histone Deacetylase Inhibitor Valproic Acid Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells
title_fullStr Histone Deacetylase Inhibitor Valproic Acid Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells
title_full_unstemmed Histone Deacetylase Inhibitor Valproic Acid Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells
title_short Histone Deacetylase Inhibitor Valproic Acid Promotes the Differentiation of Human Induced Pluripotent Stem Cells into Hepatocyte-Like Cells
title_sort histone deacetylase inhibitor valproic acid promotes the differentiation of human induced pluripotent stem cells into hepatocyte-like cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119015/
https://www.ncbi.nlm.nih.gov/pubmed/25084468
http://dx.doi.org/10.1371/journal.pone.0104010
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