Embryo development after mitochondrial supplementation from induced pluripotent stem cells
Embryo development after mitochondrial supplementation from induced pluripotent stem cells
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诱导多能干细胞补充线粒体后的胚胎发育。
DOI：
10.1007/s10815-017-0948-9
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发表时间：
2017
影响因子：
3.1
通讯作者：
Yang Dongzi
中科院分区：
文献类型：
--
作者：
Li Ruiqi;Wen Bingqiang;Zhao Haijing;Ouyang Nengyong;Ou Songbang;Wang Wenjun;Han Jianyong;Yang Dongzi
PurposeThe目的本研究的目的是评估线粒体补充（MS）对早期胚胎发育的影响，并评估MS治疗的安全性，使用诱导多能干细胞（iPSCs）作为mitochondrial donor.MethodsIn这项研究中，我们评估了MS对早期胚胎发育的影响，使用诱导多能干细胞（iPSCs）作为供体。用来自iPSC的线粒体或载体溶液注射小鼠受精卵。评价了几个参数，包括囊胚形成和植入率、E13.5胚胎和胎盘的重量、供体线粒体DNA（mtDNA）的分布、和差异甲基化区域（DMR）中的甲基化模式结果H19和Snrpn基因组的囊胚形成率和着床率以及E13.5胚胎和胎盘的重量均低于对照组。MS和对照组之间存在显著差异。此外，在MS组中的四个胎儿和所有胎盘的肌肉组织中可以检测到来自iPSC供体的mtDNA。最后，H19和SnrpnDMR的甲基化模式在MS中保持不变。结论siPSC来源的mtDNA直接参与MS后胚胎发育的过程。使用iPSC作为线粒体供体时没有观察到不良影响，但这种方法是否可以改善胚胎发育，特别是在老年小鼠中。
PurposeThe purpose of this study was to evaluate the effects of mitochondrial supplementation (MS) on early embryonic development and to assess the safety of MS treatments using induced pluripotent stem cells (iPSCs) as the mitochondrial donor.MethodsIn this study, we evaluated the effect of MS on early embryonic development using induced pluripotent stem cells (iPSCs) as the donor. Mouse zygotes were injected with either mitochondria from iPSCs or a vehicle solution. Several parameters were evaluated, including the rates of blastocyst formation and implantation, the weight of E13.5 embryos and placentas, the distribution of the donor mitochondrial DNA (mtDNA), and the pattern of methylation in the differentially methylated regions (DMRs) of theH19andSnrpngenes.ResultsWe found that neither the rates of blastocyst formation and implantation nor the weights of E13.5 embryos and placentas were significantly different between the MS and control groups. Additionally, the mtDNA from the iPSC donors could be detected in the muscle tissue of four fetuses and all placentas in the MS group. Finally, the methylation patterns ofH19andSnrpnDMRs remained unchanged by MS.ConclusionsiPSC-derived mtDNA was directly involved in the process of embryonic development after MS. No adverse effects were seen when using iPSCs as a mitochondrial donor, but it remains to be seen whether this method can improve embryonic development, especially in older mice.