Tracking the progression of the human inner cell mass during embryonic stem cell derivation

Tracking the progression of the human inner cell mass during embryonic stem cell derivation
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DOI:
10.1038/nbt.2135
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发表时间:
2012-03-01
影响因子:
46.9
通讯作者:
De Sutter, Petra
De Sutter, Petra
中科院分区:
工程技术1区
文献类型:
--
作者:
O'Leary, Thomas;Heindryckx, Bjorn;De Sutter, Petra

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体外小鼠胚胎干细胞(ESC)的不同多能状态已显示对应于小鼠胚胎发育的阶段(1-6)。对于人类细胞,关于胚胎干细胞产生之前的事件或它们是否与体内发育阶段相关知之甚少。在这里,我们调查的细胞和分子的变化,发生在过渡过程中,从人的内细胞团(ICM)的胚胎干细胞在体外。我们证明,人类胚胎干细胞起源于后ICM中间体(PICMI),一个短暂的上胚层样结构,已经历了X-失活的女性细胞,是必要的和足够的ESC衍生。PICMI是体外进行性和明确的ICM组织的结果,具有独特的细胞信号传导状态。PICMI可以冷冻保存而不损害ESC衍生能力。作为比ICM更接近ESC的祖细胞,PICMI提供了对人类干细胞多能状态的深入了解。
The different pluripotent states of mouse embryonic stem cells (ESCs) in vitro have been shown to correspond to stages of mouse embryonic development(1-6). For human cells, little is known about the events that precede the generation of ESCs or whether they correlate with in vivo developmental stages. Here we investigate the cellular and molecular changes that occur during the transition from the human inner cell mass (ICM) to ESCs in vitro. We demonstrate that human ESCs originate from a post-ICM intermediate (PICMI), a transient epiblast-like structure that has undergone X-inactivation in female cells and is both necessary and sufficient for ESC derivation. The PICMI is the result of progressive and defined ICM organization in vitro and has a distinct state of cell signaling. The PICMI can be cryopreserved without compromising ESC derivation capacity. As a closer progenitor of ESCs than the ICM, the PICMI provides insight into the pluripotent state of human stem cells.