使用Histone Deacetylase Inhibitor提高人类SCNT囊胚的效率

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Derivation of Cloned Human Blastocysts by Histone Deacetylase Inhibitor Treatment After Somatic Cell Nuclear Transfer with β-Thalassemia Fibroblasts
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来源http://www.liebertonline.com/doi/abs/10.1089/scd.2010.0451
' w# B& W: v/ ]干细胞之家Hyde翻译，转帖请注明。附上原文
1 a) A$ ]9 F4 g$ s1 r- G摘要：& {, t9 n. g  K) g
利用SCNT获得的治疗性克隆囊胚产生人类的ESC对于再生医学和以细胞为基础的药物开发有重要的意义。但是在人SCNT后形成囊胚的效率很低。对其他一些物种SCNT胚胎发育能力的研究发现使用 histone deacetylase inhibitors（组蛋白去乙酰基酶抑制剂，一种治疗癌症的新兴药物，可以导致癌细胞的细胞周期停滞……）例如TSA（曲古菌素3 H% V9 v& h; ?3 P+ V
A）处理胚胎来增加组蛋白的乙酰化可以增强胚胎的发育能力。本研究中，我们使用β-thalassemia fibroblast cells进行SCNT，在激活培养后的10h内使用5 nM TSA处理胚胎，胚胎的发育能力增强，这些胚胎发育到囊胚的效率比未经处理的胚胎要约高出2倍。我们对胚胎基因组DNA和线粒体DNA进行了指纹分析（ DNA and mitochondrial DNA fingerprinting analyses. ）以确保这些克隆胚胎确实来自于SCNT。另外，我们发现经过TSA处理的胚胎其组蛋白H3 lysine 9乙酰化增强的方式类似于IVF胚胎中观察到的现象。
) W2 W  U* {) Q2 o. H% cDerivation 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 β-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.# R2 w- P* x% p/ ~( Q0 c1 j
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再往前走走就成克隆人了……it is crazy……5 _0 A; b, d" l, g