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多能干细胞的表观遗传学景观。

Epigenetic landscape of pluripotent stem cells.

机构信息

Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

出版信息

Antioxid Redox Signal. 2012 Jul 15;17(2):205-23. doi: 10.1089/ars.2011.4375. Epub 2012 Jan 11.

DOI:10.1089/ars.2011.4375
PMID:22044221
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3353817/
Abstract

SIGNIFICANCE

Derived from the inner cell mass of the preimplantation embryo, embryonic stem cells are prototype pluripotent stem (PS) cells that have the ability of self-renewal and differentiation into almost all cell types. Exploration of the mechanisms governing this pluripotency is important for understanding reprogramming mechanisms and stem cell behavior of PS cells and can lead to enhancing reprogramming efficiency and other applications.

RECENT ADVANCES

Induced pluripotent stem cells are recently discovered PS cells that can be derived from somatic cells by overexpression of pluripotency-related transcription factors. Recent studies have shown that transcription factors and their epigenetic regulation play important roles in the generating, maintaining, and differentiating these PS cells. Recent advances in sequencing technologies allow detailed analysis of target epigenomes and microRNAs (miRs), and have revealed unique epigenetic marks and miRs for PS cells.

CRITICAL ISSUES

Epigenetic modifications of genes include histone modifications, DNA methylation, and chromatin remodeling. Working closely with epigenetic modifiers, miRs play an important role in inducing and maintaining pluripotency.

FUTURE DIRECTIONS

The dynamic changes in epigenetic marks during reprogramming and their role in cell fate changes are being uncovered. This review focuses on these new advances in the epigenetics of PS cells.

摘要

意义

胚胎干细胞来源于着床前胚胎的内细胞团,是具有自我更新和分化为几乎所有细胞类型能力的原型多能(PS)干细胞。探索调控这种多能性的机制对于理解 PS 细胞的重编程机制和干细胞行为很重要,并能提高重编程效率和其他应用。

最新进展

诱导多能干细胞是最近发现的 PS 细胞,可通过过表达多能性相关转录因子从体细胞中获得。最近的研究表明,转录因子及其表观遗传调控在产生、维持和分化这些 PS 细胞中起着重要作用。测序技术的最新进展允许对靶标表观基因组和 microRNAs(miRs)进行详细分析,并且已经揭示了 PS 细胞的独特表观遗传标记和 miRs。

关键问题

基因的表观遗传修饰包括组蛋白修饰、DNA 甲基化和染色质重塑。miRs 与表观遗传修饰物密切合作,在诱导和维持多能性方面发挥着重要作用。

未来方向

在重编程过程中,表观遗传标记的动态变化及其在细胞命运变化中的作用正在被揭示。本综述重点介绍了 PS 细胞表观遗传学的这些新进展。

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Epigenetic landscape of pluripotent stem cells.多能干细胞的表观遗传学景观。
Antioxid Redox Signal. 2012 Jul 15;17(2):205-23. doi: 10.1089/ars.2011.4375. Epub 2012 Jan 11.
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本文引用的文献

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Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development.Tet1 对于维持多能性是可有可无的,其缺失与胚胎和出生后发育是兼容的。
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Reprogramming of mouse and human cells to pluripotency using mature microRNAs.利用成熟 microRNA 对小鼠和人类细胞进行重编程为多能性细胞。
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Incomplete DNA methylation underlies a transcriptional memory of somatic cells in human iPS cells.不完全的 DNA 甲基化是人类诱导多能干细胞中体细胞转录记忆的基础。
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Highly efficient miRNA-mediated reprogramming of mouse and human somatic cells to pluripotency.高效 miRNA 介导的小鼠和人体细胞重编程为多能性。
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Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells.Tet1 和 Tet2 调节小鼠胚胎干细胞中 5-羟甲基胞嘧啶的产生和细胞谱系特化。
Cell Stem Cell. 2011 Feb 4;8(2):200-13. doi: 10.1016/j.stem.2011.01.008.
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Epigenetic modifications in pluripotent and differentiated cells.多能性和分化细胞中的表观遗传修饰。
Nat Biotechnol. 2010 Oct;28(10):1079-88. doi: 10.1038/nbt.1684.
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Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification.Tet 蛋白在 5mC 向 5hmC 的转化、胚胎干细胞自我更新和内细胞团特化中的作用。
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Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells.印迹的 Dlk1-Dio3 区域的激活与小鼠干细胞的多能性水平相关。
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