Self-renewing epiblast stem cells exhibit continual delineation of germ cells with epigenetic reprogramming in vitro
Self-renewing epiblast stem cells exhibit continual delineation of germ cells with epigenetic reprogramming in vitro
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DOI：
10.1242/dev.037747
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发表时间：
2009-11-01
期刊：
影响因子：
4.6
通讯作者：
Surani, M. Azim
中科院分区：
文献类型：
--
作者：
Hayashi, Katsuhiko;Surani, M. Azim
与来自小鼠胚泡的多能胚胎干细胞（ESC）相比，来自植入后胚胎的多能外胚层干细胞（EpiSC）表现出特征性不同的性质。然而，与ESC相比，EpiSC的特征相对较少。特别是，EpiSCs和原始生殖细胞（PGCs）之间的关系是未知的，是值得调查的，因为PGCs来源于体内植入后的上胚层细胞。我们表明，EpiSCs具有无限的能力，在维持其多能性和自我更新的条件下产生PGC。这些在体外产生的PGCs显示出适当的转录和表观遗传重编程事件，并能够进一步发育成晚期生殖细胞。值得注意的是，PGC可以反过来被诱导去分化成多能胚胎生殖细胞（EGCs），其类似于ESC而不是它们所来源的EpiSC。我们的观察结果表明，在PGC的特化过程中，内在的重编程导致在X染色体的重新激活、DNA去甲基化和关键多能性基因的重新表达之后，EpiSC的表观遗传记忆被擦除。这项研究提供了新的见解EpiSCs的性质和特性，并介绍了一个体外模型系统，将是有用的PGC规范和生殖细胞的表观遗传重编程调节机制的调查。
Pluripotent epiblast stem cells (EpiSCs) derived from postimplantation embryos exhibit properties that are characteristically different when compared with pluripotent embryonic stem cells (ESCs) derived from mouse blastocysts. However, EpiSCs are relatively less well characterised compared with ESCs. In particular, the relationship between EpiSCs and primordial germ cells (PGCs) is unknown, and is worthy of investigation because PGCs originate from postimplantation epiblast cells in vivo. We show that EpiSCs have an infinite capacity for generating PGCs, under conditions that sustain their pluripotency and self-renewal. These PGCs generated in vitro show appropriate transcriptional and epigenetic reprogramming events and are able to develop further into late germ cells. Notably, the PGCs can, in turn, be induced to undergo dedifferentiation into pluripotent embryonic germ cells (EGCs), which resemble ESCs and not the EpiSC from which they are derived. Our observations demonstrate intrinsic reprogramming during specification of PGCs that results in the erasure of epigenetic memory of EpiSCs following reactivation of the X-chromosome, DNA demethylation and re-expression of key pluripotency genes. This study provides novel insights into the nature and properties of EpiSCs, and introduces an in vitro model system that will be useful for investigations on PGC specification and on mechanisms regulating epigenetic reprogramming in germ cells.