The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification.
The ability of inner-cell-mass cells to self-renew as embryonic stem cells is acquired following epiblast specification.
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DOI：
10.1038/ncb2965
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发表时间：
2014-06
影响因子：
21.3
通讯作者：
Nichols J
中科院分区：
文献类型：
--
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
胚胎干细胞（ESC）与小鼠胚胎细胞的确切关系仍然存在争议。我们提供转录和功能数据来鉴定ESC的胚胎对应物。标记分析表明ESC与早期内细胞团（ICM）不同，与着床前外胚层非常相似。小鼠ESC的一个特点是在没有ERK信号的情况下进行传播。单细胞培养表明，当ERK通路被抑制时，细胞的自主繁殖能力在囊胚发育后期出现，并在着床后丧失。获得克隆ESC系的频率表明所有E4.5外胚层细胞都可以成为ESC。我们进一步表明，如果提供特定的层粘连蛋白底物，来自早期囊胚的ICM细胞可以发展为erk不依赖性。这些发现表明，外胚层的形成与体外培养的不依赖erk的自我更新能力以及随后作为ESC系的繁殖能力一致。
The precise relationship of embryonic stem cells (ESC) to cells in the mouse embryo remains controversial. We present transcriptional and functional data to identify the embryonic counterpart of ESC. Marker profiling shows that ESC are distinct from early inner cell mass (ICM) and closely resemble preimplantation epiblast. A characteristic feature of mouse ESC is propagation without ERK signalling. Single-cell culture reveals that cell autonomous capacity to thrive when the ERK pathway is inhibited arises late during blastocyst development and is lost after implantation. The frequency of deriving clonal ESC lines suggests that all E4.5 epiblast cells can become ESC. We further show that ICM cells from early blastocysts can progress to ERK-independence if provided with a specific laminin substrate. These findings suggest that formation of the epiblast coincides with competence for ERK-independent self-renewal in vitro and consequent propagation as ESC lines.