Derivation of Cloned Human Blastocysts by Histone Deacetylase Inhibitor Treatment After Somatic Cell Nuclear Transfer with β-Thalassemia Fibroblasts
Derivation of Cloned Human Blastocysts by Histone Deacetylase Inhibitor Treatment After Somatic Cell Nuclear Transfer with β-Thalassemia Fibroblasts
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DOI：
10.1089/scd.2010.0451
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发表时间：
2011-11-01
影响因子：
4
通讯作者：
Sun, Xiaofang
中科院分区：
文献类型：
--
作者：
Fan, Yong;Jiang, Yonghua;Sun, Xiaofang
通过体细胞核移植（SCNT）从患者特异性克隆囊胚中衍生胚胎干细胞，为再生医学和基于细胞的药物发现带来了希望。然而，人类SCNT后囊胚形成的效率非常低。在一些物种中，SCNT胚胎的发育能力已经被证明可以通过使用组蛋白去乙酰化酶抑制剂（如曲古抑素A (TSA)）来增强组蛋白乙酰化来增强。在这项研究中，我们报告了在活化培养后用5 nM TSA处理SCNT胚胎10小时，可提高由β -地中海贫血成纤维细胞构建的人SCNT胚胎的发育能力。经TSA处理的SCNT人类胚胎的囊胚形成效率约为未处理胚胎的2倍。通过DNA和线粒体DNA指纹分析证实克隆囊胚是通过SCNT产生的。此外，用TSA处理SCNT胚胎改善了组蛋白H3赖氨酸9的乙酰化，其方式与在体外受精胚胎中观察到的相似。
Derivation of embryonic stem cells from patient-specific cloned blastocysts by somatic cell nuclear transfer (SCNT) holds promise for both regenerative medicine and cell-based drug discovery. However, the efficiency of blastocyst formation after human SCNT is very low. The developmental competence of SCNT embryos has been previously demonstrated in several species to be enhanced by treatment with histone deacetylase inhibitors, such as trichostatin A (TSA), to increase histone acetylation. In this study, we report that treatment of SCNT embryos with 5 nM TSA for 10 h following activation incubation increased the developmental competence of human SCNT embryos constructed from beta-thalassemia fibroblast cells. The efficiency of blastocyst formation from SCNT human embryos treated with TSA was approximately 2 times greater than that from untreated embryos. Cloned blastocysts were confirmed to be generated through SCNT by DNA and mitochondrial DNA fingerprinting analyses. Further, treatment of SCNT embryos with TSA improved the acetylation of histone H3 at lysine 9 in a manner similar to that observed in in vitro fertilized embryos.