Derivation of pluripotent epiblast stem cells from mammalian embryos
Derivation of pluripotent epiblast stem cells from mammalian embryos
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DOI：
10.1038/nature05950
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发表时间：
2007-07-12
期刊：
影响因子：
64.8
通讯作者：
Vallier, Ludovic
中科院分区：
文献类型：
--
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
尽管第一个小鼠胚胎干细胞系是在25年前（1，2）使用基于饲养层的囊胚培养获得的，但随后将该方法扩展到其他哺乳动物（包括实验室和家养物种）的努力相对不成功。最值得注意的例外是非人灵长类动物ES细胞系的衍生（3），随后不久衍生出人ES细胞（4）。尽管小鼠和人类胚胎干细胞具有明显的共同起源和相似的多能性，但最近的研究表明，它们使用不同的信号通路来维持其多能性状态。小鼠ES细胞依赖于白血病抑制因子和骨形态发生蛋白，而它们的人类对应物依赖于激活素（INHBA）/结节（NODAL）和成纤维细胞生长因子（FGF）。在这里，我们表明，多能干细胞可以来自植入后的小鼠和大鼠胚胎的晚期外胚层，使用化学成分确定的，含有激活素的培养基，足以长期维持人类胚胎干细胞。我们的研究结果表明，激活素/Nodal信号转导在这些新型干细胞的多能性的衍生和维持中具有进化上保守的作用。外胚层干细胞提供了一个有价值的实验系统，以确定小鼠和人类胚胎干细胞之间的区别是否反映了物种差异或不同的时间起源。
Although the first mouse embryonic stem (ES) cell lines were derived 25 years ago(1,2) using feeder-layer-based blastocyst cultures, subsequent efforts to extend the approach to other mammals, including both laboratory and domestic species, have been relatively unsuccessful. The most notable exceptions were the derivation of non-human primate ES cell lines(3) followed shortly thereafter by their derivation of human ES cells(4). Despite the apparent common origin and the similar pluripotency of mouse and human embryonic stem cells, recent studies have revealed that they use different signalling pathways to maintain their pluripotent status. Mouse ES cells depend on leukaemia inhibitory factor and bone morphogenetic protein, whereas their human counterparts rely on activin (INHBA)/nodal (NODAL) and fibroblast growth factor (FGF). Here we show that pluripotent stem cells can be derived from the late epiblast layer of post-implantation mouse and rat embryos using chemically defined, activin-containing culture medium that is sufficient for long-term maintenance of human embryonic stem cells. Our results demonstrate that activin/Nodal signalling has an evolutionarily conserved role in the derivation and the maintenance of pluripotency in these novel stem cells. Epiblast stem cells provide a valuable experimental system for determining whether distinctions between mouse and human embryonic stem cells reflect species differences or diverse temporal origins.