The Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery, University of Cambridge, Cambridge, United Kingdom.
Stem Cells. 2012 Feb;30(2):161-8. doi: 10.1002/stem.793.
Mouse epiblast stem cells (EpiSCs) derived from postimplantation embryos are developmentally and functionally different from embryonic stem cells (ESCs) generated from blastocysts. EpiSCs require Activin A and FGF2 signaling for self-renewal, similar to human ESCs (hESCs), while mouse ESCs require LIF and BMP4. Unlike ESCs, EpiSCs have undergone X-inactivation, similar to the tendency of hESCs. The shared self-renewal and X-inactivation properties of EpiSCs and hESCs suggest that they have an epigenetic state distinct from ESCs. This hypothesis predicts that EpiSCs would have monoallelic expression of most imprinted genes, like that observed in hESCs. Here, we confirm this prediction. By contrast, we find that mouse induced pluripotent stem cells (iPSCs) tend to lose imprinting similar to mouse ESCs. These findings reveal that iPSCs have an epigenetic status associated with their pluripotent state rather than their developmental origin. Our results also reinforce the view that hESCs and EpiSCs are in vitro counterparts, sharing an epigenetic status distinct from ESCs and iPSCs.
鼠类胚外内胚层干细胞（EpiSCs）来源于着床后的胚胎，在发育和功能上与囊胚来源的胚胎干细胞（ESCs）不同。EpiSCs 自我更新需要激活素 A 和 FGF2 信号，类似于人类胚胎干细胞（hESCs），而鼠类 ESCs 需要 LIF 和 BMP4。与 ESCs 不同，EpiSCs 经历了 X 染色体失活，类似于 hESCs 的趋势。EpiSCs 和 hESCs 共同的自我更新和 X 染色体失活特性表明它们具有不同于 ESCs 的表观遗传状态。这一假设预测 EpiSCs 会像 hESCs 一样表现出大多数印记基因的单等位基因表达。在这里，我们证实了这一预测。相比之下，我们发现鼠类诱导多能干细胞（iPSCs）倾向于失去印记，类似于鼠类 ESCs。这些发现表明 iPSCs 具有与多能状态相关的表观遗传状态，而不是其发育起源。我们的结果也进一步证实了 hESCs 和 EpiSCs 是体外对应物的观点，它们具有不同于 ESCs 和 iPSCs 的表观遗传状态。
