内蒙古大学发《Nature》文章 干细胞多能性的获得

　　

生物通报道，Wellcome Trust研究所，剑桥大学Gurdon癌症研究所，内蒙古大学生命科学院，林肯研究中心等多处的科学家在外胚层细胞多能性的研究方面获得新的进展，相关文章Epigenetic reversion of post-implantation epiblast to pluripotent embryonic stem cells发表在最新一期的Nature杂志上。

 

文章通讯作者是Wellcome Trust研究所，剑桥大学的M. Azim Surani教授，主要从事遗传重编程和表观遗传学方面的研究。第二作者是来自内蒙古大学生命科学院的李喜和教授（英国剑桥大学兼职研究员），主要从事生殖生物学方面的研究。

 

在胚胎发育过程中，囊胚期胚胎的原始外胚层细胞在发育前具有多能性，随后在发育中逐步失去多能性。在这过程中，发生了表观遗传学方面的改变，包括DNA甲基化的改变，X染色体的变化等。

 

现在，研究人员发现，来自5.5-7.5天的小鼠胚胎的外胚层细胞，可通过暴露于LIF/STAT3信号作用而被重新编程回到多能状态。研究发现获得多能性的同时它们在转录组（细胞中的全部mRNA）也随着发生了相应的变化，这些变化导致外胚层细胞中的表型记忆和外遗传记忆的丧失，DNA甲基化情况发生变化，X染色体被激活，钙粘蛋白的表达发生变化。

 

以这种方式重新编程的细胞可分化成体细胞组织和生殖细胞，但却与能够自我更新的外胚层干细胞不同。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。

 

研究者下一的计划将深入了解引发重编程的信号转导机制。

（生物通 小茜）

 Letter

Nature 461, 1292-1295 (29 October 2009) | doi:10.1038/nature08534; Received 8 December 2008; Accepted 28 September 2009; Published online 8 October 2009

 

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

 

Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK

College of Life Science, Inner Mongolia University/Mengniu RB CO. Ltd., West No. 1 Daxue Road, Huhhot, Inner Mongolia 010021, China

Molecular Cell Biology, Applied Biosystems, 850 Lincoln Centre Drive, Foster City, California 94404, USA

These authors contributed equally to this work.

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. (Email: [e-mail]).

 

【Abstract】

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.

 

李喜和，1984年毕业于内蒙古大学生物系，获学士学位。1994年毕业于日本东京农业大学获畜产学博士学位。博士、教授，现任蒙牛繁育生物技术有限公司技术总监，英国剑桥大学兼职研究员，中国农业大学讲座教授，内蒙古大学兼职教授。