Aggregation of pre‐implantation embryos improves establishment of parthenogenetic stem cells and expression of imprinted genes
Aggregation of pre‐implantation embryos improves establishment of parthenogenetic stem cells and expression of imprinted genes
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DOI：
10.1111/j.1440-169x.2012.01335.x
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发表时间：
2012-05
期刊：
影响因子：
4.6
通讯作者：
Zhi-Yan Shan;Yanshuang Wu;Xing-hui Shen;Xue Li;Yuan Xue;Zhong Zheng;Zhen-dong Wang;Chun-Jia Liu;Ruizhen Sun;Zhao-yuan Li;Jing-ling Shen;Zhong-hua Liu;Lei Lei-Lei
中科院分区：
文献类型：
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作者：
Zhi-Yan Shan;Yanshuang Wu;Xing-hui Shen;Xue Li;Yuan Xue;Zhong Zheng;Zhen-dong Wang;Chun-Jia Liu;Ruizhen Sun;Zhao-yuan Li;Jing-ling Shen;Zhong-hua Liu;Lei Lei-Lei
孤雌生殖胚胎干细胞（PgES）是研究基因组印迹的一个重要的体外模型系统。然而，PgES细胞的分化潜能是有限的。这可能是由于PgES细胞与受精胚胎干细胞（fES）相比，其异质性较低，导致大多数印迹基因的表达不同。在这里，我们描述了通过聚集8-细胞阶段的孤雌胚胎（aPgES细胞）建立PgES细胞，这可能会增加杂合性。我们发现，aPgES细胞的衍生与内细胞团细胞的数量增加，通过聚集是更有效的比PgES细胞从一个单一的孤雌胚泡。aPgES细胞具有正常核型，碱性磷酸酶染色阳性，表达高水平的ES细胞标志物，并可分化为由三个胚层组成的畸胎瘤。与PgES细胞相比，aPgES细胞中父系印迹基因表达量明显增加，而aPg囊胚中则没有这种变化。这表明，聚集诱导效应可以改变父系表达的印迹基因的表达。我们的研究表明，aPgES细胞，其中比PgES细胞更接近fES细胞的印迹基因的表达，将有助于所有器官和避免免疫排斥反应，这可能为再生医学提供宝贵的材料。
Parthenogenetic embryonic stem cells (PgES) might advance cell replacement therapies and provide a valuable in vitro model system to study the genomic imprinting. However, the differential potential of PgES cells was limited. It could result from relative low heterology of PgES cells compared with ES cells from fertilization (fES), which produce different expression of most imprinted genes. Here, we described the establishment of PgES cells by aggregating parthenogenetic embryos at the 8‐cell stage (aPgES cells), which may increase heterozygy. We found that derivation of aPgES cells in association with an increased number of inner cell mass cells by aggregating was more efficient than that of PgES cells from a single parthenogenetic blastocyst. The aPgES cells have normal karyotype, stain positive for alkaline phosphatase, express high levels of ES cell markers and can differentiate into teratomas composed of the three germ layers. Moreover, compared with PgES cells, the more highly upregulated paternally expressed imprinted genes were observed in aPgES cells, the same change was not shown in aPg blastocysts. This suggested that the aggregation induced effect could modify the expression of paternally expressed imprinted genes. Our studies showed that aPgES cells, the expression of imprinted genes in which more closely resemble fES cells than PgES cells, would contribute to all organs and avoiding immuno‐rejection, which may provide invaluable material for regeneration medicine.