Alternative dominance of the parental genomes in hybrid cells generated through the fusion of mouse embryonic stem cells with fibroblasts.

Alternative dominance of the parental genomes in hybrid cells generated through the fusion of mouse embryonic stem cells with fibroblasts.
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DOI:
10.1038/s41598-017-18352-4
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发表时间:
2017-12-22
期刊:
影响因子:
4.6
通讯作者:
Serov OL
Serov OL
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Matveeva NM;Fishman VS;Zakharova IS;Shevchenko AI;Pristyazhnyuk IE;Menzorov AG;Serov OL

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首次将小鼠胚胎干细胞(ES)与成纤维细胞融合,获得了具有类ES细胞和类成纤维细胞两种表型的杂种细胞。对亲本细胞中差异表达的2,848个基因的转录组分析表明,这些基因中的34-43%在杂交细胞中表达,与其表型一致;这些基因中的25-29%显示中等水平的表达,并且这些基因中的12-16%维持在亲本细胞水平的表达,与杂交细胞的表型不一致。大约20%的分析基因显示出与双亲不同的意想不到的表达模式。观察到一个不寻常的现象,即Xist表达的非法激活和近四倍体成纤维细胞样杂交细胞中两个X染色体之一的失活,而两个X在ES细胞样杂交细胞体外分化前后都是活跃的。这些结果和以前的异核体上获得的数据表明,具有成纤维细胞样表型的杂交细胞的出现反映了在体细胞伴侣的影响下ES细胞基因组的重编程,而不是诱导分化。
For the first time, two types of hybrid cells with embryonic stem (ES) cell-like and fibroblast-like phenotypes were produced through the fusion of mouse ES cells with fibroblasts. Transcriptome analysis of 2,848 genes differentially expressed in the parental cells demonstrated that 34–43% of these genes are expressed in hybrid cells, consistent with their phenotypes; 25–29% of these genes display intermediate levels of expression, and 12–16% of these genes maintained expression at the parental cell level, inconsistent with the phenotype of the hybrid cell. Approximately 20% of the analyzed genes displayed unexpected expression patterns that differ from both parents. An unusual phenomenon was observed, namely, the illegitimate activation of Xist expression and the inactivation of one of two X-chromosomes in the near-tetraploid fibroblast-like hybrid cells, whereas both Xs were active before and after in vitro differentiation of the ES cell-like hybrid cells. These results and previous data obtained on heterokaryons suggest that the appearance of hybrid cells with a fibroblast-like phenotype reflects the reprogramming, rather than the induced differentiation, of the ES cell genome under the influence of a somatic partner.
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