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人类胚胎植入前发育过程中的早期转录激活和多能性程序启动的波动。

Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development.

机构信息

Center for Regenerative Medicine in Barcelona, CMR[B], Dr Aiguader 88, 08003, Barcelona, Spain.

出版信息

Development. 2011 Sep;138(17):3699-709. doi: 10.1242/dev.064741. Epub 2011 Jul 20.

Abstract

The events regulating human preimplantation development are still largely unknown owing to a scarcity of material, ethical and legal limitations and a lack of reliable techniques to faithfully amplify the transcriptome of a single cell. Nonetheless, human embryology is gathering renewed interest due to its close relationship with both stem cell biology and epigenetic reprogramming to pluripotency and their importance in regenerative medicine. Carefully timed genome-wide transcript analyses of single oocytes and embryos uncovered a series of successive waves of embryonic transcriptional initiation that start as early as the 2-cell stage. In addition, we identified the hierarchical activation of genes involved in the regulation of pluripotency. Finally, we developed HumER, a database of human preimplantation gene expression, to serve the scientific community. Importantly, our work links early transcription in the human embryo with the correct execution of the pluripotency program later in development and paves the way for the identification of factors to improve epigenetic reprogramming.

摘要

由于材料稀缺、伦理和法律限制以及缺乏可靠的技术来真实放大单个细胞的转录组,调节人类胚胎着床前发育的事件在很大程度上仍然未知。尽管如此,由于人类胚胎学与干细胞生物学和多能性的表观遗传重编程密切相关,以及其在再生医学中的重要性,它再次引起了人们的兴趣。对单个卵母细胞和胚胎进行的精心定时全基因组转录分析揭示了一系列早期胚胎转录起始的连续波,这些波早在 2 细胞阶段就开始了。此外,我们还确定了参与多能性调控的基因的层次激活。最后,我们开发了 HumER,这是一个人类胚胎着床前基因表达数据库,为科学界服务。重要的是,我们的工作将人类胚胎早期的转录与后期多能性程序的正确执行联系起来,并为鉴定改善表观遗传重编程的因素铺平了道路。

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