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

Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development
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DOI:
10.1242/dev.064741
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发表时间:
2011-09-01
期刊:
影响因子:
4.6
通讯作者:
Izpisua Belmonte, Juan Carlos
Izpisua Belmonte, Juan Carlos
中科院分区:
生物学2区
文献类型:
--
作者:
Vassena, Rita;Boue, Stephanie;Izpisua Belmonte, Juan Carlos

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由于缺乏材料、伦理和法律的限制以及缺乏可靠的技术来忠实地扩增单个细胞的转录组,调节人类植入前发育的事件在很大程度上仍然是未知的。尽管如此,人类胚胎学正在收集新的兴趣,由于其与干细胞生物学和表观遗传重编程多能性及其在再生医学中的重要性的密切关系。对单个卵母细胞和胚胎的全基因组转录分析发现,早在2细胞阶段就开始了一系列连续的胚胎转录起始波。此外,我们确定了参与调节多能性的基因的分级激活。最后,我们开发了人类胚胎植入前基因表达数据库HumER,以服务于科学界。重要的是,我们的工作将人类胚胎中的早期转录与发育后期多能性程序的正确执行联系起来,并为识别改善表观遗传重编程的因素铺平了道路。
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.