X-inactivation status varies in human embryonic stem cell lines

X-inactivation status varies in human embryonic stem cell lines
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DOI:
10.1634/stemcells.2004-0371
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发表时间:
2005-11-01
期刊:
影响因子:
5.2
通讯作者:
Carpenter, MK
Carpenter, MK
中科院分区:
医学2区
文献类型:
--
作者:
Hoffman, LM;Hall, L;Carpenter, MK

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源自人类囊胚的人类胚胎干细胞(hESCs)具有明显的无限增殖能力,并且能够分化为外胚层、中胚层和内胚层。因此,人类胚胎干细胞系在细胞替代疗法中具有巨大的应用潜力。然而,首先必须证明人类胚胎干细胞保持稳定的核型和表型,并且基因表达受到适当调控。到目前为止,不同的人类胚胎干细胞系表现出与多能细胞相关的标志物的相似表达模式。然而,对人类胚胎干细胞系的表观遗传状态的评估最近才刚刚开始。表观遗传基因调控的一个例子是哺乳动物雌性中X染色体的剂量补偿。这是通过一种被称为X染色体失活(XCI)的表观遗传事件实现的,该事件在细胞分化时启动。我们提供了第一个证据,即未分化的人类胚胎干细胞系表现出不同的X染色体失活模式。《干细胞》2005年;23卷:1468 - 1478页
Human embryonic stem cells (hESCs) derived from human blastocysts have an apparently unlimited proliferative capacity and can differentiate into ectoderm, mesoderm, and endoderm. As such, hESC lines have enormous potential for use in cell replacement therapies. It must first be demonstrated, however, that hESCs maintain a stable karyotype and phenotype and that gene expression is appropriately regulated. To date, different hESC lines exhibit similar patterns of expression of markers associated with pluripotent cells. However, the evaluation of epigenetic status of hESC lines has only recently been initiated. One example of epigenetic gene regulation is dosage compensation of the X chromosome in mammalian females. This is achieved through an epigenetic event referred to as X-chromosome inactivation (XCI), an event initiated upon cellular differentiation. We provide the first evidence that undifferentiated hESC lines exhibit different patterns of XCI. STEM CELLS 2005;23:1468-1478.