Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei

Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei
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DOI:
10.1073/pnas.192433399
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发表时间:
2002-10-01
影响因子:
11.1
通讯作者:
Jaenisch, R
Jaenisch, R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Humphreys, D;Eggan, K;Jaenisch, R

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为了评估克隆中基因表达异常的程度,我们通过微阵列分析了来自胚胎干细胞和新鲜分离的卵丘细胞的核移植(NT)克隆小鼠的胎盘和肝脏的RNA的整体基因表达。对10,000多个基因表达谱的直接比较表明,对于两种供体细胞类型,NT胎盘中约4%的表达基因的表达水平与对照显著不同,大多数异常表达的基因在两种类型的克隆中都是共同的。然而,重要的是,胚胎干细胞和卵丘细胞来源的克隆之间有一组较小的基因表达不同。克隆小鼠的肝脏也显示出与胎盘不同的基因表达异常,尽管程度较小,而且受影响的基因集也不同。我们的结果表明,克隆中经常出现基因表达异常,其中大多数表达异常似乎是NT程序中常见的,而其他表达异常似乎反映了特定的供体核。
To assess the extent of abnormal gene expression in clones, we assessed global gene expression by microarray analysis on RNA from the placentas and livers of neonatal cloned mice derived by nuclear transfer (NT) from both cultured embryonic stem cells and freshly isolated cumulus cells. Direct comparison of gene expression profiles of more than 10,000 genes showed that for both donor cell types approximate to4% of the expressed genes in the NT placentas differed dramatically in expression levels from those in controls and that the majority of abnormally expressed genes were common to both types of clones. Importantly, however, the expression of a smaller set of genes differed between the embryonic stem cell- and cumulus cell-derived clones. The livers of the cloned mice also showed abnormal gene expression, although to a lesser extent, and with a different set of affected genes, than seen in the placentas. Our results demonstrate frequent abnormal gene expression in clones, in which most expression abnormalities appear common to the NT procedure whereas others appear to reflect the particular donor nucleus.