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Harnessing the HDAC-histone deacetylase enzymes, inhibitors and how these can be utilised in tissue engineering.
International Journal of Oral Science ( IF 10.8 ) Pub Date : 2019-06-10 , DOI: 10.1038/s41368-019-0053-2
Liam Lawlor 1, 2 , Xuebin B Yang 1, 2
Affiliation  

There are large knowledge gaps regarding how to control stem cells growth and differentiation. The limitations of currently available technologies, such as growth factors and/or gene therapies has led to the search of alternatives. We explore here how a cell’s epigenome influences determination of cell type, and potential applications in tissue engineering. A prevalent epigenetic modification is the acetylation of DNA core histone proteins. Acetylation levels heavily influence gene transcription. Histone deacetylase (HDAC) enzymes can remove these acetyl groups, leading to the formation of a condensed and more transcriptionally silenced chromatin. Histone deacetylase inhibitors (HDACis) can inhibit these enzymes, resulting in the increased acetylation of histones, thereby affecting gene expression. There is strong evidence to suggest that HDACis can be utilised in stem cell therapies and tissue engineering, potentially providing novel tools to control stem cell fate. This review introduces the structure/function of HDAC enzymes and their links to different tissue types (specifically bone, cardiac, neural tissues), including the history, current status and future perspectives of using HDACis for stem cell research and tissue engineering, with particular attention paid to how different HDAC isoforms may be integral to this field.



中文翻译:

利用HDAC-组蛋白脱乙酰基酶,抑制剂以及它们在组织工程中的利用方式。

关于如何控制干细胞的生长和分化,存在很大的知识空白。当前可用技术(例如生长因子和/或基因疗法)的局限性导致人们寻找替代方案。我们在这里探讨细胞的表观基因组如何影响细胞类型的确定以及在组织工程中的潜在应用。普遍的表观遗传修饰是DNA核心组蛋白的乙酰化。乙酰化水平严重影响基因转录。组蛋白脱乙酰基酶(HDAC)酶可以去除这些乙酰基,从而导致缩合且在转录上更沉默的染色质的形成。组蛋白脱乙酰基酶抑制剂(HDACis)可以抑制这些酶,导致组蛋白乙酰化增加,从而影响基因表达。有强有力的证据表明,HDACis可用于干细胞疗法和组织工程中,有可能提供控制干细胞命运的新工具。这篇综述介绍了HDAC酶的结构/功能及其与不同组织类型(特别是骨骼,心脏,神经组织)的联系,包括使用HDACis进行干细胞研究和组织工程的历史,现状和未来观点,尤其要注意考虑到如何将不同的HDAC同工型整合到该领域。

更新日期:2019-06-10
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