组蛋白去乙酰化酶抑制剂调控干细胞分化与体细胞重编程的研究进展

Progress in histone deacetylase inhibitor regulation of stem cell differentiation and somatic reprogramming

表观遗传调控,如组蛋白乙酰化修饰,是决定干细胞分化方向的重要机制。组蛋白去乙酰化酶抑制剂(HDACi)通过影响不同亚类的组蛋白去乙酰化酶(HDAC)活性,提高组蛋白乙酰化水平,调控基因表达,从而影响胚胎干细胞自我更新,以及沿神经元、心肌和造血等细胞谱系的定向分化。HDACi类小分子化合物在体细胞重编程中也有广泛的应用,可替代致癌因子c-Myc和Klf4,促进体细胞克隆。研究显示,HDACi的效应与药物剂量、细胞类型和细胞分化状态密切相关。本文主要阐述了HDACi在干细胞分化和体细胞重编程中的应用进展,并对所涉及的分子通路进行讨论,有助于揭示干细胞定向分化的关键分子机制,优化干细胞定向分化诱导策略,对干细胞诱导分化具有重要的理论和实用价值。

Epigenetic regulation,such as histone acetylation,is an important mechanism that determines the direction of stem cell differentiation.Histone deacetylase inhibitors(HDACi)affect the histone deacetylase(HDAC)activity in different subclasses,increase the level of histone acetylation and regulate gene expression,thus,the self-renewal of embryonic stem cell(ESC)and the directional differentiation of ESC along the cell lines of neurons,myocardium and hematopoietic cells were affected.HDACi-like small molecules are also widely used in somatic cell reprogramming,which can replace c-Myc and Klf4 and promote somatic cell cloning.Studies have shown that the effect of HDACi is closely related to drug dose,cell type and cell differentiation.This review focuses on the application of HDACi in stem cell differentiation and reprogramming,and moreover discusses the molecular pathways involved,which can help to reveal the key molecular mechanism of directional differentiation and optimize the induction strategy of directional differentiation of stem cells,it is of great value to the induction and differentiation of stem cells.