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文化对多能干细胞和植入前胚胎表观遗传特性的影响。

The impact of culture on epigenetic properties of pluripotent stem cells and pre-implantation embryos.

机构信息

Medical Research Council Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, U.K.

出版信息

Biochem Soc Trans. 2013 Jun;41(3):711-9. doi: 10.1042/BST20130049.

DOI:10.1042/BST20130049
PMID:23697930
Abstract

Cultured pluripotent stem cells hold great promise for regenerative medicine. Considerable efforts have been invested into the refinement and definition of improved culture systems that sustain self-renewal and avoid differentiation of pluripotent cells in vitro. Recent studies have, however, found that the choice of culture condition has a significant impact on epigenetic profiles of cultured pluripotent cells. Mouse and human ESCs (embryonic stem cells) show substantial epigenetic differences that are dependent on the culture condition, including global changes to DNA methylation and histone modifications and, in female human ESCs, to the epigenetic process of X chromosome inactivation. Epigenetic perturbations have also been detected during culture of pre-implantation embryos; limited research undertaken in mouse suggests a direct effect of the in vitro environment on epigenetic processes in this system. Widespread epigenetic changes induced by the culture condition in stem cells thus emphasize the necessity for extensive research into both immediate and long-term epigenetic effects of embryo culture during assisted reproductive technologies.

摘要

培养的多能干细胞为再生医学带来了巨大的希望。人们投入了大量的精力来改进和定义改进的培养系统,以维持多能细胞的自我更新并避免其在体外分化。然而,最近的研究发现,培养条件的选择对培养的多能干细胞的表观遗传特征有显著影响。小鼠和人类胚胎干细胞(embryonic stem cells,ESCs)显示出显著的表观遗传差异,这些差异取决于培养条件,包括 DNA 甲基化和组蛋白修饰的全局变化,以及在女性人类 ESCs 中 X 染色体失活的表观遗传过程。在胚胎培养过程中也检测到了表观遗传干扰;在小鼠中进行的有限研究表明,体外环境对该系统中的表观遗传过程有直接影响。因此,培养条件诱导的干细胞中广泛的表观遗传变化强调了在辅助生殖技术中对胚胎培养的即时和长期表观遗传效应进行广泛研究的必要性。

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