产品号 #72282_C
表观遗传修饰剂；抑制组蛋白去乙酰化酶 (HDAC)1 和 HDAC6
总览
曲古抑菌素 A（Trichostatin A）一种强效且可逆的组蛋白去乙酰化酶 (HDAC) 抑制剂，因此可通过阻止组蛋白尾部赖氨酸残基乙酰基的去除发挥表观遗传修饰作用。曲古抑菌素 A 可抑制 I 类和 II 类 HDAC，包括 HDAC1 (IC₅₀ = 6 nM)、HDAC4 (IC₅₀ = 38 nM) 和 HDAC6 (IC₅₀ = 8.6 nM)。(Furumai et al.; Yoshida et al.)
重编程
·提高小鼠胚胎成纤维细胞重编程为诱导多能干细胞 (iPS) 的效率（Huangfu et al.）。
·与 5-氮杂胞苷联合使用，可重置小鼠 iPS 细胞的表观遗传记忆（Kim et al.）。
·通过体细胞核移植提高克隆小鼠胚胎发育效率（Kishigami et al.）。
维持和自我更新
·防止培养大鼠原代肝细胞去分化，维持肝脏特异性细胞功能（Henkens et al.）。
分化
·促进人间充质干细胞向肝细胞分化（Snykers et al.）。
细胞类型
肝细胞，间充质干/祖细胞，多能干细胞
种属
人，小鼠，非人灵长类，其它细胞系，大鼠
应用
分化，培养，重编程
研究领域
上皮细胞研究，干细胞生物学
CAS 编号
58880-19-6
化学式
C₁₇H₂₂N₂O₃
纯度
≥ 95 %
通路
表观遗传学
靶点
HDAC
Protocols and Documentation
Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.
Applications
This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.
Resources and Publications
Educational Materials (3)
Publications (7)
Epigenetic memory in induced pluripotent stem cells. Nature 2010 SEP
Abstract
Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.
Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds Nat Biotechnol 2008
Abstract
Reprogramming of mouse and human somatic cells can be achieved by ectopic expression of transcription factors, but with low efficiencies. We report that DNA methyltransferase and histone deacetylase (HDAC) inhibitors improve reprogramming efficiency. In particular, valproic acid (VPA), an HDAC inhibitor, improves reprogramming efficiency by more than 100-fold, using Oct4-GFP as a reporter. VPA also enables efficient induction of pluripotent stem cells without introduction of the oncogene c-Myc.
Trichostatin A, a critical factor in maintaining the functional differentiation of primary cultured rat hepatocytes. Toxicology and applied pharmacology 2007 JAN
Abstract
Histone deacetylase inhibitors (HDI) have been shown to increase differentiation-related gene expression in several tumor-derived cell lines by hyperacetylating core histones. Effects of HDI on primary cultured cells, however, have hardly been investigated. In the present study, the ability of trichostatin A (TSA), a prototype hydroxamate HDI, to counteract the loss of liver-specific functions in primary rat hepatocyte cultures has been investigated. Upon exposure to TSA, it was found that the cell viability of the cultured hepatocytes and their albumin secretion as a function of culture time were increased. TSA-treated hepatocytes also better maintained cytochrome P450 (CYP)-mediated phase I biotransformation capacity, whereas the activity of phase II glutathione S-transferases (GST) was not affected. Western blot and qRT-PCR analysis of CYP1A1, CYP2B1 and CYP3A11 protein and mRNA levels, respectively, further revealed that TSA acts at the transcriptional level. In addition, protein expression levels of the liver-enriched transcription factors (LETFs) hepatic nuclear factor 4 alpha (HNF4alpha) and CCAAT/enhancer binding protein alpha (C/EBPalpha) were accordingly increased by TSA throughout culture time. In conclusion, these findings indicate that TSA plays a major role in the preservation of the differentiated hepatic phenotype in culture. It is suggested that the effects of TSA on CYP gene expression are mediated via controlling the expression of LETFs.
更多信息
| Species | Human, Mouse, Non-Human Primate, Other, Rat |
|---|---|
| Cas Number | 58880-19-6 |
| Chemical Formula | C₁₇H₂₂N₂O₃ |
| Purity | ≥ 95% |
| Target | HDAC |
| Pathway | Epigenetic |
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