Histone deacetylase inhibitors improve in vitro and in vivo developmental competence of somatic cell nuclear transfer porcine embryos.
Histone deacetylase inhibitors improve in vitro and in vivo developmental competence of somatic cell nuclear transfer porcine embryos.
复制标题
DOI：
10.1089/cell.2009.0038
复制
发表时间：
2010-02
影响因子：
1.6
通讯作者：
Prather RS
中科院分区：
文献类型：
--
作者：
Zhao J;Hao Y;Ross JW;Spate LD;Walters EM;Samuel MS;Rieke A;Murphy CN;Prather RS
体细胞核的表观遗传重编程可能是通过体细胞核移植（SCNT）产生的所有哺乳动物中观察到的低成功率的主要原因。已经证明，通过处理组蛋白脱乙酰酶抑制剂（HDACi）（如阿司他丁A（TSA））以增加组蛋白乙酰化，几个物种中SCNT胚胎的发育能力显著增强。在这里，我们报告说，50 nM TSA激活后10小时增加了猪SCNT胚胎构建从长白猪胎儿成纤维细胞（FFCs）在体外和体内的发育能力，但不是在更高的浓度。因此，我们优化了另一种新型HDACi Scriptaid在猪SCNT胚胎发育中的应用。我们发现，与未处理组相比，当远交的长白猪FFC和耳成纤维细胞（EFC）用作供体时，500 nM Scriptaid处理显著增强了SCNT胚胎发育至囊胚阶段。Scriptaid将长白猪FFC的总体克隆效率从0.4%（未处理组）提高到1.6%，长白猪EFC的总体克隆效率从0%提高到3.7%。此外，用Scriptaid处理SCNT胚胎改善了组蛋白H4上赖氨酸8（AcH4K8）的组蛋白乙酰化，其模式与体外受精（IVF）胚胎相似。
Faulty epigenetic reprogramming of somatic nuclei is likely to be a major cause of low success observed in all mammals produced through somatic cell nuclear transfer (SCNT). It has been demonstrated that the developmental competence of SCNT embryos in several species were significantly enhanced via treatment of histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA) to increase histone acetylation. Here we report that 50 nM TSA for 10 hrs after activation increased the developmental competence of porcine SCNT embryos constructed from Landrace fetal fibroblast cells (FFCs) in vitro and in vivo, but not at higher concentrations. Therefore we optimized the application of another novel HDACi, Scriptaid, for development of porcine SCNT embryos. We found that treatment with 500 nM Scriptaid significantly enhanced the development SCNT embryos to the blastocyst stage when outbred Landrace FFCs and ear fibroblast cells (EFCs) were used as donors compared to the untreated group. Scriptaid increased the overall cloning efficiency from 0.4% (untreated group) to 1.6% for Landrace FFCs and 0% to 3.7% for Landrace EFCs. Moreover, treatment of SCNT embryos with Scriptaid improved the histone acetylation on Histone H4 at lysine 8 (AcH4K8) in a pattern similar to that of the in vitro fertilized (IVF) embryos.
登录
查看更多内容
影响因子：
3.6
作者：
Hao, Yanhong;Mathialagan, Nagappan;Prather, Randall S.
通讯作者：
Prather, Randall S.
影响因子：
46.9
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
通讯作者：
Melton, Douglas A.
DOI：
10.1089/clo.2008.0072
发表时间：
2009-03-01
期刊：
CLONING AND STEM CELLS
影响因子：
--
作者：
Meng, Qinggang;Polgar, Zsuzsanna;Dinnyes, Andras
通讯作者：
Dinnyes, Andras
影响因子：
3.6
作者：
Hao, YH;Lai, LX;Prather, RS
通讯作者：
Prather, RS
DOI：
10.1073/pnas.192433399
发表时间：
2002-10-01
影响因子：
11.1
作者：
Humphreys, D;Eggan, K;Jaenisch, R
通讯作者：
Jaenisch, R