Effects of trichostatin A and PXD101 on the in vitro development of mouse somatic cell nuclear transfer embryos

Effects of trichostatin A and PXD101 on the in vitro development of mouse somatic cell nuclear transfer embryos
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曲古抑菌素A和PXD101对小鼠体细胞核移植胚胎体外发育的影响

DOI:
10.1089/cell.2016.0030
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发表时间:
2017
影响因子:
1.6
通讯作者:
Yuemin Li
Yuemin Li
中科院分区:
医学4区
文献类型:
--
作者:
Xiaoyan Qiu;Haihong You;Xiong Xiao;Nan Li;Yuemin Li

文献摘要

被引文献

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体细胞核移植(SCNT)克隆动物的成功率低,被认为与异常的表观遗传核重编程有关。已经证明,用组蛋白脱乙酰酶抑制剂(HDACis)处理增强了SCNT胚胎的发育潜力。以前在许多物种中的研究表明,用HDACi-the.in在这项研究中,我们将两种不同的SCNT方案与TSA进行了比较,并首次研究了另一种新型HDACi PXD 101(贝利司他)对小鼠SCNT胚胎体外发育的影响。在激活期间(6小时)和激活后(4小时)用5 nM TSA处理的小鼠SCNT胚胎中的囊胚发育率(39.1%)或在活化期间(6小时)和活化后(4小时)使用50 nM PXD 101(40.2%)显著高于未处理的SCNT胚胎(11.5%),与未治疗组相比,两种治疗也显著改善了NT-ESCs的后续建立(38.1%和40.9% vs. 11.8%)。总之,我们优化了TSA浓度和处理时机,并首次研究了PXD 101对小鼠SCNT胚胎发育和NT-ESCs建立的影响。
The low success rate of animal cloning by somatic cell nuclear transfer (SCNT) is believed to be associated with aberrant epigenetic nuclear reprogramming. It has been demonstrated that treatment with histone deacetylase inhibitors (HDACis) enhances developmental potential of SCNT embryos. Previous studies in many species revealed that treatment of SCNT embryos with trichostatin A (TSA)—an HDACi—significantly enhances the.in vitro development of SCNT embryos. In this study, we compared two different SCNT protocols with TSA and investigate, for the first time, the effect of another new HDACi, PXD101 (belinostat), on in vitro development of mouse SCNT embryo. Rates of blastocyst development in mouse SCNT embryos treated with either 5 nM TSA during (6 hours) and after (4 hours) activation (39.1%) or with 50nM PXD101 during (6 hours) and after (4 hours) activation (40.2%) were significantly higher than those of nontreated SCNT embryos (11.5%) and both treatments also significantly improved the subsequent establishment of NT-ESCs in comparison with the nontreated group (38.1% and 40.9% vs. 11.8%). In conclusion, we optimized the TSA concentration and treatment timing and, for the first time, investigated the effect of PXD101 on mouse development of SCNT embryos and establishment of NT-ESCs.