State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
J Biol Chem. 2010 Oct 1;285(40):31002-10. doi: 10.1074/jbc.M110.136085. Epub 2010 Jun 21.
Somatic cell nuclear transfer (SCNT) has shown tremendous potential for understanding the mechanisms of reprogramming and creating applications in the realms of agriculture, therapeutics, and regenerative medicine, although the efficiency of reprogramming is still low. Somatic nucleus reprogramming is triggered in the short time after transfer into recipient cytoplasm, and therefore, this period is regarded as a key stage for optimizing SCNT. Here we report that CBHA, a histone deacetylase inhibitor, modifies the acetylation status of somatic nuclei and increases the developmental potential of mouse cloned embryos to reach pre- and post-implantation stages. Furthermore, the cloned embryos treated by CBHA displayed higher efficiency in the derivation of nuclear transfer embryonic stem cell lines by promoting outgrowths. More importantly, CBHA increased blastocyst quality compared with trichostatin A, another prevalent histone deacetylase inhibitor reported previously. Use of CBHA should improve the productivity of SCNT for a variety of research and clinical applications, and comparisons of cells with different levels of pluripotency and treated with CBHA versus trichostatin A will facilitate studies of the mechanisms of reprogramming.
体细胞核移植（Somatic cell nuclear transfer，SCNT）在理解重编程机制和在农业、治疗学和再生医学领域创造应用方面显示出巨大的潜力，尽管重编程的效率仍然很低。体细胞核在转移到受体细胞质后的短时间内被触发重新编程，因此，这一时期被认为是优化 SCNT 的关键阶段。在这里，我们报告说，组蛋白去乙酰化酶抑制剂 CBHA 修饰了体细胞核的乙酰化状态，并增加了小鼠克隆胚胎的发育潜力，使其达到了植入前和植入后阶段。此外，用 CBHA 处理的克隆胚胎通过促进外生体的生长，在核转移胚胎干细胞系的衍生中表现出更高的效率。更重要的是，与先前报道的另一种常见的组蛋白去乙酰化酶抑制剂曲古抑菌素 A（trichostatin A）相比，CBHA 提高了囊胚的质量。使用 CBHA 应该可以提高 SCNT 在各种研究和临床应用中的生产力，并且对具有不同多能性水平的细胞进行比较，并与曲古抑菌素 A 进行比较，将有助于研究重编程的机制。
