Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells.
The multi-potentiality of mesenchymal stem cells makes them excellent options for future tissue engineering and clinical therapy, including liver injury. In this study, we investigated the effects of valproic acid (VPA), a direct inhibitor of histone deacetylase (HDAC), on the hepatic differentiatio...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3642107?pdf=render |
| _version_ | 1818778117830868992 |
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| author | Xuejun Dong Ruolang Pan Hui Zhang Chao Yang Jianzhong Shao Lixin Xiang |
| author_facet | Xuejun Dong Ruolang Pan Hui Zhang Chao Yang Jianzhong Shao Lixin Xiang |
| author_sort | Xuejun Dong |
| collection | DOAJ |
| description | The multi-potentiality of mesenchymal stem cells makes them excellent options for future tissue engineering and clinical therapy, including liver injury. In this study, we investigated the effects of valproic acid (VPA), a direct inhibitor of histone deacetylase (HDAC), on the hepatic differentiation of human bone marrow mesenchymal stem cells (BMMSCs). The cells were found to differentiate into a more homogeneous hepatocyte-like population when pretreated with 5 mM VPA for 72 h. The expression of liver-specific markers was significantly upregulated in the VPA-treated group at the mRNA and protein levels. VPA treatment also significantly enhanced the hepatic functions of the differentiated cells, including glycogen storage, cytochrome P450 activity, AFP and ALB synthesis, and urea production. Further analysis showed that treatment with 5 mM of VPA for 72 h greatly improved the histones H3 and H4 acetylation. These results demonstrated that VPA could considerably improve the hepatic differentiation of human BMMSCs, probably because the chromatin-acetylated state changes upon VPA treatment through its HDAC inhibitory effect. Thus, this study provides a direct research model for producing human hepatocytes for clinical purposes. |
| first_indexed | 2024-12-18T11:39:38Z |
| format | Article |
| id | doaj.art-7a8c711594774fd9803e5daabfb51d90 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T11:39:38Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-7a8c711594774fd9803e5daabfb51d902022-12-21T21:09:27ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6340510.1371/journal.pone.0063405Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells.Xuejun DongRuolang PanHui ZhangChao YangJianzhong ShaoLixin XiangThe multi-potentiality of mesenchymal stem cells makes them excellent options for future tissue engineering and clinical therapy, including liver injury. In this study, we investigated the effects of valproic acid (VPA), a direct inhibitor of histone deacetylase (HDAC), on the hepatic differentiation of human bone marrow mesenchymal stem cells (BMMSCs). The cells were found to differentiate into a more homogeneous hepatocyte-like population when pretreated with 5 mM VPA for 72 h. The expression of liver-specific markers was significantly upregulated in the VPA-treated group at the mRNA and protein levels. VPA treatment also significantly enhanced the hepatic functions of the differentiated cells, including glycogen storage, cytochrome P450 activity, AFP and ALB synthesis, and urea production. Further analysis showed that treatment with 5 mM of VPA for 72 h greatly improved the histones H3 and H4 acetylation. These results demonstrated that VPA could considerably improve the hepatic differentiation of human BMMSCs, probably because the chromatin-acetylated state changes upon VPA treatment through its HDAC inhibitory effect. Thus, this study provides a direct research model for producing human hepatocytes for clinical purposes.http://europepmc.org/articles/PMC3642107?pdf=render |
| spellingShingle | Xuejun Dong Ruolang Pan Hui Zhang Chao Yang Jianzhong Shao Lixin Xiang Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells. PLoS ONE |
| title | Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells. |
| title_full | Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells. |
| title_fullStr | Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells. |
| title_full_unstemmed | Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells. |
| title_short | Modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells. |
| title_sort | modification of histone acetylation facilitates hepatic differentiation of human bone marrow mesenchymal stem cells |
| url | http://europepmc.org/articles/PMC3642107?pdf=render |
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