Mitochondrial DNA transmission and transcription after somatic cell fusion to one or more cytoplasts
Mitochondrial DNA transmission and transcription after somatic cell fusion to one or more cytoplasts
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DOI：
10.1634/stemcells.2007-0747
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
John, Justin C. St.
中科院分区：
文献类型：
--
作者：
Bowles, Emma J.;Tecirlioglu, R. Tayfur;John, Justin C. St.
受精后，线粒体DNA从卵母细胞遗传并以同质性方式传递。然而，在核移植后，线粒体DNA可以从供体细胞和受体卵母细胞传递，导致异质性状态。为了确定供体细胞和受体细胞质线粒体DNA之间的遗传多样性是否影响发育，我们通过将供体细胞与一个或多个去核细胞质融合来产生牛胚胎。对胚胎、胎儿组织和后代血液样本的线粒体DNA分析显示，来自两个或三个细胞质的早期着床前胚胎的线粒体DNA变异比胎儿组织显着更多。使用单胞质产生的胚胎的系统发育分析将线粒体DNA序列变体分成三个独立的组，其与供体细胞系具有不同数量的遗传差异。在异质组织和血液样本中，主要的线粒体DNA群体与供体细胞的差异比频率较低的等位基因更大。此外，分析的同源编码的细胞色素B基因表明，两个异质等位基因编码不同的氨基酸，和线粒体DNA/mRNA的比例为每个等位基因的组织之间的差异显着。供体细胞和细胞质之间的进化距离的程度和组织之间的异质性的变化可能会产生影响，更不同的属间核转移和使用这种方法产生胚胎干细胞。
Following fertilization, mitochondrial DNA is inherited from the oocyte and transmitted homoplasmically. However, following nuclear transfer, mitochondrial DNA can be transmitted from both the donor cell and recipient oocyte, resulting in a state of heteroplasmy. To determine whether the genetic diversity between donor cell and recipient cytoplast mitochondrial DNA influences development, we generated bovine embryos by fusing a donor cell to one or more enucleated cytoplasts. Analysis of mitochondrial DNA from embryos, fetal tissues, and blood samples from offspring revealed that early preimplantation embryos from two or three cytoplasts had significantly more mitochondrial DNA variants than fetal tissues. Phylogenic analysis of embryos generated using single cytoplasts divided the mitochondrial DNA sequence variants into three separate groups with various amounts of genetic divergence from the donor cell line. In heteroplasmic tissue and blood samples, the predominant mitochondrial DNA population was significantly more divergent from the donor cell than the less frequent allele. Furthermore, analysis of the mitochondrially encoded cytochrome B gene showed that two heteroplasmic alleles encoded for different amino acids, and the ratios of mitochondrial DNA/mRNA for each allele differed significantly between tissues. The degree of evolutionary distance between the donor cell and the cytoplast and the variability in heteroplasmy between tissues may have an impact on more divergent intergeneric nuclear transfer and the use of this approach for the generation of embryonic stem cells.