Department of Stem Cell and Regenerative Biotechnology, Konkuk Institute of Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Korea.
Research Center of Integrative Cellulomics, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
Int J Mol Sci. 2019 Oct 31;20(21):5428. doi: 10.3390/ijms20215428.
Pluripotent stem cells can be established from parthenogenetic embryos, which only possess maternal alleles with maternal-specific imprinting patterns. Previously, we and others showed that parthenogenetic embryonic stem cells (pESCs) and parthenogenetic induced pluripotent stem cells (piPSCs) progressively lose the bimaternal imprinting patterns. As ESCs and iPSCs are naïve pluripotent stem cells, parthenogenetic primed pluripotent stem cells have not yet been established, and thus, their imprinting patterns have not been studied. Here, we first established parthenogenetic epiblast stem cells (pEpiSCs) from 7.5 dpc parthenogenetic implantation embryos and compared the expression patterns and DNA methylation status of the representative imprinted genes with biparental EpiSCs. We found that there were no striking differences between pEpiSCs and biparental EpiSCs with respect to morphology, pluripotency gene expression, and differentiation potential, but there were differences in the expression and DNA methylation status of imprinted genes (, , , and ). Moreover, pEpiSCs displayed a different DNA methylation pattern compared with that of parthenogenetic neural stem cells (pNSCs), which showed a typical bimaternal imprinting pattern. These results suggest that both naïve pluripotent stem cells and primed pluripotent stem cells have an unstable imprinting status.
多能干细胞可从仅具有母源等位基因且具有母源特异性印迹模式的孤雌胚胎中建立。先前,我们和其他人表明,孤雌胚胎干细胞 (pESC) 和孤雌诱导多能干细胞 (piPSC) 逐渐丧失双母源印迹模式。由于 ESC 和 iPSC 是原始多能干细胞,因此尚未建立原始的孤雌多能干细胞,因此尚未研究其印迹模式。在这里,我们首次从 7.5 dpc 的孤雌胚胎着床胚胎中建立了孤雌上胚层干细胞 (pEpiSC),并比较了具有双亲本 EpiSC 的代表性印迹基因的表达模式和 DNA 甲基化状态。我们发现,pEpiSC 与双亲本 EpiSC 在形态、多能性基因表达和分化潜能方面没有明显差异,但印迹基因的表达和 DNA 甲基化状态存在差异(、、、和)。此外,pEpiSC 显示出与孤雌神经干细胞 (pNSC) 不同的 DNA 甲基化模式,后者显示出典型的双母源印迹模式。这些结果表明,原始和原始多能干细胞都具有不稳定的印迹状态。