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中华细胞与干细胞杂志(电子版) ›› 2020, Vol. 10 ›› Issue (02) : 115 -118. doi: 10.3877/cma.j.issn.2095-1221.2020.02.008

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综述

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
何泽诏1, 翁晓菲1   
  1. 1. 410013 长沙,湖南师范大学医学院
  • 收稿日期:2019-08-30 出版日期:2020-04-01
  • 基金资助:
    国家自然科学基金(81870201)

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

Zezhao He1, Xiaofei Weng1   

  1. 1. School of Medicine, Hunan Normal University, Changsha 410013, China
  • Received:2019-08-30 Published:2020-04-01
  • About author:
    Corresponding author:Li Tao, Email:
引用本文:

何泽诏, 翁晓菲. 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[J/OL]. 中华细胞与干细胞杂志(电子版), 2020, 10(02): 115-118.

Zezhao He, Xiaofei Weng. Progress in histone deacetylase inhibitor regulation of stem cell differentiation and somatic reprogramming[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2020, 10(02): 115-118.

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.

[1]
Karmodiya K, Krebs AR, Oulad-Abdelghani M, et al. H3K9 and H3K14 acetylation co-occur at many gene regulatory elements, while H3K14ac marks a subset of inactive inducible promoters in mouse embryonic stem cells[J]. BMC Genomics, 2012, 13:424.
[2]
Roche J, Bertrand P. Inside HDACs with more selective HDAC inhibitors[J]. Eur J Med Chem, 2016, 121:451-483.
[3]
Li Y, Seto E. HDACs and HDAC inhibitors in cancer development and therapy[J]. Cold Spring Harb Perspect Med, 2016, 6(10). pii: a026831.
[4]
Montgomery RL, Davis CA, Potthoff MJ, et al. Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility[J]. Genes Dev, 2007, 21(14):1790-1802.
[5]
Ceccacci E, Minucci S. Inhibition of histone deacetylases in cancer therapy: lessons from leukaemia[J]. Br J Cancer, 2016, 114(6):605-611.
[6]
Acampora D, Di Giovannantonio LG, Garofalo A, et al. Functional antagonism between OTX2 and NANOG specifies a spectrum of heterogeneous identities in embryonic stem cells[J]. Stem Cell Reports, 2017, 9(5):1642-1659.
[7]
Turinetto V, Giachino C. Histone variants as emerging regulators of embryonic stem cell identity[J]. Epigenetics, 2015, 10(7):563-573.
[8]
Karantzali E, Schulz H, Hummel O, et al. Histone deacetylase inhibition accelerates the early events of stem cell differentiation: transcriptomic and epigenetic analysis[J]. Genome Biol, 2008, 9(4):R65.
[9]
Ware CB, Wang L, Mecham BH, et al. Histone deacetylase inhibition elicits an evolutionarily conserved Self-Renewal program in embryonic stem cells[J]. Cell Stem Cell, 2009, 4(4):359-369.
[10]
Shi GL, Gao FR, Jin Y. The regulatory role of histone deacetylase inhibitors in Fgf4 expression is dependent on the differentiation state of pluripotent stem cells[J]. J Cell Physiol, 2011, 226(12):3190-3196.
[11]
Tie K, Wu M, Deng Y, et al. Histone hypo-acetylation of Sox9 mediates nicotine-induced weak cartilage repair by suppressing BMSC chondrogenic differentiation[J]. Stem Cell Res Ther, 2018, 9(1):98.
[12]
Bradley EW, Carpio LR, Van Wijnen AJ, et al. Histone deacetylases in bone development and skeletal disorders[J]. Physiol Rev, 2015, 95(4):1359-1381.
[13]
Xu S, De Veirman K, Evans H, et al. Effect of the HDAC inhibitor vorinostat on the osteogenic differentiation of mesenchymal stem cells in vitro and bone formation in vivo[J]. Acta Pharmacol Sin, 2013, 34(5):699-709.
[14]
Adamik J, Jin S, Sun Q, et al. EZH2 or HDAC1 inhibition reverses multiple myeloma-induced epigenetic suppression of osteoblast differentiation[J]. Mol Cancer Res, 2017, 15(4):405-417.
[15]
Hu XQ, Zhang X, Dai LH, et al. Histone deacetylase inhibitor trichostatin a promotes the osteogenic differentiation of rat Adipose-Derived stem cells by altering the epigenetic modifications on Runx2 promoter in a BMP Signaling-Dependent manner[J]. Stem Cells Dev, 2013, 22(2):248-255.
[16]
Zhang L, Jin M, Margariti A, et al. Sp1-dependent activation of HDAC7 is required for platelet-derived growth Factor-BB-induced smooth muscle cell differentiation from stem cells[J]. J Biol Chem, 2010, 285(49):38463-38472.
[17]
Tang Y, Boucher JM, Liaw L. Histone deacetylase activity selectively regulates notch-mediated smooth muscle differentiation in human vascular cells[J]. J Am Heart Assoc, 2012, 1(3):e000901.
[18]
Foulquier S, Daskalopoulos EP, Lluri G, et al. WNT signaling in cardiac and vascular disease[J]. Pharmacol Rev, 2018, 70(1):68-141.
[19]
Jun JY, Yang, Qian, et al. Histone deacetylases and cardiovascular cell lineage commitment[J]. World J Stem Cells, 2015, 7(5):852-858.
[20]
Kawamura T, Ono K, Morimoto T, et al. Acetylation of GATA-4 is involved in the differentiation of embryonic stem cells into cardiac myocytes[J]. J Biol Chem, 2005, 280(20):19682-19688.
[21]
Arcidiacono OA, Krejí J, Suchánková J, et al. Deacetylation of histone H4 accompanying cardiomyogenesis is weakened in HDAC1-depleted ES cells[J]. Int J Mol Sci, 2018, 19(8). pii: E2425.
[22]
Ko S, Russell JO, Tian J, et al. Hdac1 regulates differentiation of bipotent liver progenitor cells during regeneration via Sox9b and Cdk8[J]. Gastroenterology, 2019, 156(1):187-202.e14.
[23]
Noël ES, Casal-Sueiro A, Busch-Nentwich E, et al. Organ-specific requirements for Hdac1 in liver and pancreas formation[J]. Dev Biol, 2008, 322(2):237-250.
[24]
Plaster N, Sonntag C, Schilling TF, et al. REREa/atrophin-2 interacts with histone deacetylase and Fgf8 signaling to regulate multiple processes of zebrafish development[J]. Dev Dyn, 2007, 236(7):1891-1904.
[25]
Raut A, Khanna A. Enhanced expression of hepatocyte-specific microRNAs in valproic acid mediated hepatic trans-differentiation of human umbilical cord derived mesenchymal stem cells[J]. Exp Cell Res, 2016, 343(2):237-247.
[26]
Ren M, Yan L, Shang CZ, et al. Effects of Sodium butyrate on the differentiation of pancreatic and hepatic progenitor cells from mouse embryonic stem cells[J]. J Cell Biochem, 2010, 109(1):236-244.
[27]
Hsieh J, Zhao X. Genetics and epigenetics in adult neurogenesis[J]. Cold Spring Harb Perspect Biol, 2016, 8(6). pii: a018911.
[28]
Katayama S, Morii A, Makanga JO, et al. HDAC8 regulates neural differentiation through embryoid body formation in P19 cells[J]. Biochem Biophys Res Commun, 2018, 498(1):45-51.
[29]
Qiao YB, Wang R, Yang XF, et al. Dual roles of histone H3 lysine 9 acetylation in human embryonic stem cell pluripotency and neural differentiation[J]. J Biol Chem, 2015, 290(4):2508-2520.
[30]
Wilting RH, Yanover E, Heideman MR, et al. Overlapping functions of Hdac1 and Hdac2 in cell cycle regulation and haematopoiesis[J]. EMBO J, 2010, 29(15):2586-2597.
[31]
Bug G, Gül H, Schwarz K, et al. Valproic acid stimulates proliferation and self-renewal of hematopoietic stem cells[J]. Cancer Res, 2005, 65(7):2537-2541.
[32]
Yamamura K, Ohishi K, Katayama N, et al. Pleiotropic role of histone deacetylases in the regulation of human adult erythropoiesis[J]. Br J Haematol, 2006, 135(2):242-253.
[33]
Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006, 126(4):663-676.
[34]
Huangfu D, Maehr R, Guo WJ, et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds[J]. Nat Biotechnol, 2008, 26(7):795-797.
[35]
Chen X, Zhai YY, Yu DH, et al. Valproic acid enhances iPSC induction from human bone Marrow-Derived cells through the suppression of Reprogramming-Induced senescence[J]. J Cell Physiol, 2016, 231(8):1719-1727.
[36]
Saini M, Selokar NL, Revey T, et al. Trichostatin a alters the expression of cell cycle controlling genes and microRNAs in donor cells and subsequently improves the yield and quality of cloned bovine embryos in vitro[J]. Theriogenology, 2014, 82(7):1036-1042.
[37]
Mao J, Zhang Q, Deng W, et al. Epigenetic modifiers facilitate induction and pluripotency of porcine iPSCs[J]. Stem Cell Reports, 2017, 8(1):11-20.
[38]
Huan Y, Zhu J, Huang B, et al. Trichostatin a rescues the disrupted imprinting induced by somatic cell nuclear transfer in pigs[J]. PLoS One, 2015, 10(5):e0126607.
[39]
Jin JX, Lee S, Taweechaipaisankul A, et al. The HDAC inhibitor LAQ824 enhances epigenetic reprogramming and in vitro development of porcine SCNT embryos[J]. Cell Physiol Biochem, 2017, 41(3):1255-1266.
[40]
Song YR, Hai T, Wang Y, et al. Epigenetic reprogramming, gene expression and in vitro development of porcine SCNT embryos are significantly improved by a histone deacetylase inhibitor-m-carboxycinnamic acid bishydroxamide (CBHA)[J]. Protein Cell, 2014, 5(5):382-393.
[41]
Zviran A, Mor N, Rais Y, et al. Deterministic somatic cell reprogramming involves continuous transcriptional changes governed by Myc and epigenetic-driven modules[J]. Cell Stem Cell, 2019, 24(2):328-341.e9.
[42]
Xu W, Li Z, Yu B, et al. Effects of DNMT1 and HDAC inhibitors on gene-specific methylation reprogramming during porcine somatic cell nuclear transfer[J]. PLoS One, 2013, 8(5):e64705.
[43]
Liao HF, Mo CF, Wu SC, et al. Dnmt3l-knockout donor cells improve somatic cell nuclear transfer reprogramming efficiency[J]. Reproduction, 2015, 150(4):245-256.
[44]
Liu Z, Cai Y, Wang Y, et al. Cloning of macaque monkeys by somatic cell nuclear transfer[J]. Cell, 2018, 172(4):881-887.
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