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外胚层细胞重新获得干细胞特性的方法
分类:国际医学技术 来源:本站编辑部 作者:med00 职称:
摘要:
这项工作为研究信号作用和外遗传重新编程会怎样促进多能性的重新获得提供了一个模型。

受精卵经过卵裂被分割成很多小细胞,这些由小细胞组成的中空球形体称为囊胚。囊胚细胞迁移、转变形成原肠胚,由三层细胞层构成:外胚层(ectoderm)、中胚层(mesoderm)、内胚层(endoderm)。细胞首次在囊胚期胚胎的原始外胚层细胞中形成的多能状态,在随后的发育中会失去。

 

 

 

 

 

现在,Bao等人发现,来自形成时间已长达7.5天的小鼠胚胎的高级植入后外胚层细胞,可通过暴露于LIF/STAT3信号作用而被重新编程回到多能状态。它们在转录组(细胞中的全部mRNA)中发现了伴随的变化,这些变化导致见于外胚层细胞中的表型记忆和外遗传记忆的丧失。以这种方式重新编程的细胞会形成银鲛的体细胞组织和生殖细胞,与能够自我更新的外胚层干细胞不同。

原始出处:

Nature 461, 1292-1295 (29 October 2009) | doi:10.1038/nature08534

Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells near-final version

Siqin Bao1,4, Fuchou Tang1,4, Xihe Li2, Katsuhiko Hayashi1,5, Astrid Gillich1, Kaiqin Lao3 & M. Azim Surani1

1 Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK
2 College of Life Science, Inner Mongolia University/Mengniu RB CO. Ltd., West No. 1 Daxue Road, Huhhot, Inner Mongolia 010021, China
3 Molecular Cell Biology, Applied Biosystems, 850 Lincoln Centre Drive, Foster City, California 94404, USA
4 These authors contributed equally to this work.
5 Present address: Department of Anatomy and Cell Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-Cho, Sako-Ku, Kyoto 606-8501, Japan.
Correspondence to: M. Azim Surani1 Correspondence and requests for materials should be addressed to M.A.S.

The pluripotent state, which is first established in the primitive ectoderm cells of blastocysts, is lost progressively and irreversibly during subsequent development1. For example, development of post-implantation epiblast cells from primitive ectoderm involves significant transcriptional and epigenetic changes, including DNA methylation and X chromosome inactivation2, which create a robust epigenetic barrier and prevent their reversion to a primitive-ectoderm-like state. Epiblast cells are refractory to leukaemia inhibitory factor (LIF)–STAT3 signalling, but they respond to activin/basic fibroblast growth factor to form self-renewing epiblast stem cells (EpiSCs), which exhibit essential properties of epiblast cells3, 4 and that differ from embryonic stem (ES) cells derived from primitive ectoderm5. Here we show reprogramming of advanced epiblast cells from embryonic day 5.5–7.5 mouse embryos with uniform expression of N-cadherin and inactive X chromosome to ES-cell-like cells (rESCs) in response to LIF–STAT3 signalling. Cultured epiblast cells overcome the epigenetic barrier progressively as they proceed with the erasure of key properties of epiblast cells, resulting in DNA demethylation, X reactivation and expression of E-cadherin. The accompanying changes in the transcriptome result in a loss of phenotypic and epigenetic memory of epiblast cells. Using this approach, we report reversion of established EpiSCs to rESCs. Moreover, unlike epiblast and EpiSCs, rESCs contribute to somatic tissues and germ cells in chimaeras. Further studies may reveal how signalling-induced epigenetic reprogramming may promote reacquisition of pluripotency. 

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浏览次数:7088次   发布日期:2009-12-24

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