组蛋白去乙酰化酶抑制剂丙戊酸对骨骼肌细胞发育的影响。
Effects of histone deacetylase inhibitor valproic acid on skeletal myocyte development.
作者信息
Li Qiao, Foote Michelle, Chen Jihong
机构信息
1] Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada [2] Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
出版信息
Sci Rep. 2014 Nov 26;4:7207. doi: 10.1038/srep07207.
The tight interaction between genomic DNA and histones, which normally represses gene transcription, can be relaxed by histone acetylation. This loosening of the DNA-histone complex is important for selective gene activation during stem cell differentiation. Histone acetylation may be increased through the application of histone deacetylase inhibitors at the early stages of differentiation to modulate lineage commitment. We examined the effects of the histone deacetylase inhibitor valproic acid on the differentiation of pluripotent stem cells into skeletal myocytes. Our data demonstrated that valproic acid can act in concert with retinoic acid to enhance the commitment of stem cells into the skeletal myocyte lineage reinforcing the notion that histone acetylation is important for skeletal myogenesis. Thus, using a combination of small molecules to exploit different signaling pathways pertaining to specific gene programs will allow for modulation of lineage specification and stem cell differentiation in potential cell-based therapies.
基因组DNA与组蛋白之间紧密的相互作用通常会抑制基因转录，而组蛋白乙酰化可使其松弛。DNA-组蛋白复合物的这种松弛对于干细胞分化过程中的选择性基因激活很重要。在分化早期应用组蛋白脱乙酰酶抑制剂可增加组蛋白乙酰化，从而调节细胞谱系定向。我们研究了组蛋白脱乙酰酶抑制剂丙戊酸对多能干细胞向骨骼肌细胞分化的影响。我们的数据表明，丙戊酸可与视黄酸协同作用，增强干细胞向骨骼肌细胞谱系的定向，强化了组蛋白乙酰化对骨骼肌生成很重要这一观点。因此，在潜在的细胞疗法中，使用小分子组合来利用与特定基因程序相关的不同信号通路，将能够调节细胞谱系特化和干细胞分化。
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