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人类胚胎干细胞中X染色体失活的表观遗传调控。

Epigenetic regulation of X-inactivation in human embryonic stem cells.

作者信息

Dvash Tamar, Fan Guoping

机构信息

Department of Human Genetics and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, David Geffen School of Medicine, University of California at Los Angeles, 90095, USA.

出版信息

Epigenetics. 2009 Jan;4(1):19-22. doi: 10.4161/epi.4.1.7438. Epub 2009 Jan 17.

DOI:10.4161/epi.4.1.7438
PMID:19106643
Abstract

X chromosome inactivation (XCI) allows dosage compensation of the expression from sex chromosome in mammalian female cells. Although this mechanism is extensively studied in the mouse model organism, the corresponding mechanism during human development is largely unknown. The generation of human embryonic stem cells (hESCs) provides an invaluable tool to address early embryogenesis in humans. Even though hESCs were supposed to shed light on the XCI process in early human embryogenesis, previous studies largely indicated inconsistency in the status of XCI in these cells. Recently, new data suggested that in vitro culture might affect epigenetic mechanisms such as XCI. In this review we will present the existing data regarding XCI variations in hESC as compared to data from the mouse embryo and embryonic stem cells. We will also suggest possible explanations for the conflicting observations in the literature regarding XCI in hESCs.

摘要

X染色体失活(XCI)可实现哺乳动物雌性细胞中性染色体表达的剂量补偿。尽管在小鼠模式生物中对该机制进行了广泛研究,但人类发育过程中的相应机制在很大程度上仍不清楚。人类胚胎干细胞(hESC)的产生为研究人类早期胚胎发育提供了一个极其宝贵的工具。尽管hESC本应有助于阐明人类早期胚胎发育中的XCI过程,但先前的研究在很大程度上表明这些细胞中XCI的状态不一致。最近,新数据表明体外培养可能会影响诸如XCI等表观遗传机制。在本综述中,我们将呈现与小鼠胚胎和胚胎干细胞数据相比,关于hESC中XCI变异的现有数据。我们还将对文献中关于hESC中XCI的相互矛盾的观察结果提出可能的解释。

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Epigenetic regulation of X-inactivation in human embryonic stem cells.人类胚胎干细胞中X染色体失活的表观遗传调控。
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2
X-inactivation in female human embryonic stem cells is in a nonrandom pattern and prone to epigenetic alterations.女性人类胚胎干细胞中的X染色体失活呈非随机模式,且易于发生表观遗传改变。
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引用本文的文献

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High-resolution chromosomal microarray analysis of early-stage human embryonic stem cells reveals an association between X chromosome instability and skewed X inactivation.早期人类胚胎干细胞的高分辨率染色体微阵列分析揭示了X染色体不稳定性与X染色体失活偏态之间的关联。
Cell Biosci. 2014 Dec 2;4(1):74. doi: 10.1186/2045-3701-4-74. eCollection 2014.
2
XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells.XACT,一种长链非编码转录本,覆盖人类多能干细胞中的活性 X 染色体。
Nat Genet. 2013 Mar;45(3):239-41. doi: 10.1038/ng.2530. Epub 2013 Jan 20.
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Transducing bioelectric signals into epigenetic pathways during tadpole tail regeneration.
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Anat Rec (Hoboken). 2012 Oct;295(10):1541-51. doi: 10.1002/ar.22495. Epub 2012 Aug 29.
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Solving the "X" in embryos and stem cells.解决胚胎和干细胞中的“X”问题。
Stem Cells Dev. 2012 May 20;21(8):1215-24. doi: 10.1089/scd.2011.0685. Epub 2012 Mar 6.
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Concise review: Pluripotency and the transcriptional inactivation of the female Mammalian X chromosome.简明综述:多能性与雌性哺乳动物 X 染色体的转录失活。
Stem Cells. 2012 Jan;30(1):48-54. doi: 10.1002/stem.755.
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