New cell lines from mouse epiblast share defining features with human embryonic stem cells

New cell lines from mouse epiblast share defining features with human embryonic stem cells
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DOI:
10.1038/nature05972
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发表时间:
2007-07-12
期刊:
影响因子:
64.8
通讯作者:
McKay, Ronald D. G.
McKay, Ronald D. G.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Tesar, Paul J.;Chenoweth, Josh G.;McKay, Ronald D. G.

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人类胚胎干细胞(ES)在医学和生物学中的应用与了解起始细胞群有着内在的依赖性。人类胚胎干细胞与小鼠胚胎干细胞不同,两种细胞类型的具体胚胎起源尚不清楚。先前的研究表明,小鼠ES细胞只能从植入子宫前的胚胎中获得(1-5)。在这里,我们表明,细胞系可以来自外胚层,一种组织的植入后胚胎,产生胚胎本身。这些细胞,我们称之为EpiSC(植入后上胚层衍生的干细胞),表达已知调节多能性的转录因子,保持其基因组完整性,并稳健地分化为主要的体细胞类型以及原始生殖细胞。EpiSC系在其表观遗传状态和控制其分化的信号方面与小鼠ES细胞不同。此外,EpiSC和人ES细胞共享通常在上胚层中起作用的基因表达和信号应答模式。这些结果表明,上胚层细胞可以保持稳定的细胞系,并询问了解多能细胞如何在早期发育过程中产生不同的命运。
The application of human embryonic stem (ES) cells in medicine and biology has an inherent reliance on understanding the starting cell population. Human ES cells differ from mouse ES cells and the specific embryonic origin of both cell types is unclear. Previous work suggested that mouse ES cells could only be obtained from the embryo before implantation in the uterus(1-5). Here we show that cell lines can be derived from the epiblast, a tissue of the post-implantation embryo that generates the embryo proper. These cells, which we refer to as EpiSCs (post-implantation epiblast-derived stem cells), express transcription factors known to regulate pluripotency, maintain their genomic integrity, and robustly differentiate into the major somatic cell types as well as primordial germ cells. The EpiSC lines are distinct from mouse ES cells in their epigenetic state and the signals controlling their differentiation. Furthermore, EpiSC and human ES cells share patterns of gene expression and signalling responses that normally function in the epiblast. These results show that epiblast cells can be maintained as stable cell lines and interrogated to understand how pluripotent cells generate distinct fates during early development.