Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres.
Comparison of epigenetic mediator expression and function in mouse and human embryonic blastomeres.
复制标题
DOI：
10.1093/hmg/ddu212
复制
发表时间：
2014-09-15
影响因子：
3.5
通讯作者：
Reijo Pera RA
中科院分区：
文献类型：
--
作者：
Chavez SL;McElroy SL;Bossert NL;De Jonge CJ;Rodriguez MV;Leong DE;Behr B;Westphal LM;Reijo Pera RA
人类胚胎发育的地图，结合成像，分子，遗传和表观遗传数据与其他物种和跨病理学进行比较，将大大有利于基础科学和临床应用。在这里，我们比较了小鼠和人类胚胎，可育/不育夫妇的胚胎，以及补充生长因子后，DNA甲基化和组蛋白修饰的关键介质的mRNA和蛋白质表达。我们观察到，小鼠和人类胚胎个体的特征在于DNA甲基化和组蛋白修饰模式的相似性和明显差异，特别是在单细胞水平上。特别是，虽然小鼠胚胎首先表现出不同的组蛋白修饰的亚区室化之间的桑椹胚阶段的卵裂球和囊胚中的细胞亚群，差异组蛋白修饰的表达之间的卵裂球早期在人类胚胎中的四到八个细胞的阶段。同样，在可育和不育夫妇的胚胎之间也观察到表观遗传介质表达的差异，这在很大程度上是均衡的，以响应生长因子的补充，这表明选择生长因子可能会防止在长期胚胎培养过程中表观遗传谱的改变。最后，我们确定，通过吗啉代技术的一个单一的组蛋白修饰酶，Rps 6 ka 4/Msk 2，减少表达，导致裂解阶段逮捕评估延时成像，并与非整倍体的产生。两者合计，数据文件的差异，物种之间的表观遗传模式与生育力的影响，并建议在植入前发育过程中的个人表观遗传因素的功能作用。
A map of human embryo development that combines imaging, molecular, genetic and epigenetic data for comparisons to other species and across pathologies would be greatly beneficial for basic science and clinical applications. Here, we compared mRNA and protein expression of key mediators of DNA methylation and histone modifications between mouse and human embryos, embryos from fertile/infertile couples, and following growth factor supplementation. We observed that individual mouse and human embryos are characterized by similarities and distinct differences in DNA methylation and histone modification patterns especially at the single-cell level. In particular, while mouse embryos first exhibited sub-compartmentalization of different histone modifications between blastomeres at the morula stage and cell sub-populations in blastocysts, differential histone modification expression was detected between blastomeres earlier in human embryos at the four- to eight-cell stage. Likewise, differences in epigenetic mediator expression were also observed between embryos from fertile and infertile couples, which were largely equalized in response to growth factor supplementation, suggesting that select growth factors might prevent alterations in epigenetic profiles during prolonged embryo culture. Finally, we determined that reduced expression via morpholino technologies of a single histone-modifying enzyme, Rps6ka4/Msk2, resulted in cleavage-stage arrest as assessed by time-lapse imaging and was associated with aneuploidy generation. Taken together, data document differences in epigenetic patterns between species with implications for fertility and suggest functional roles for individual epigenetic factors during pre-implantation development.
登录
查看更多内容
影响因子：
1.2
作者：
Golding, MC;Westhusin, ME
通讯作者：
Westhusin, ME
影响因子：
6.7
作者：
Anderson, Richard A.;Bayne, Rosemary A. L.;De Sousa, Paul A.
通讯作者：
De Sousa, Paul A.
影响因子：
10.5
作者：
Jedrusik, Agnieszka;Parfitt, David-Emlyn;Zernicka-Goetz, Magdalena
通讯作者：
Zernicka-Goetz, Magdalena
影响因子：
3.8
作者：
Fulka, H;Mrazek, M;Fulka, J
通讯作者：
Fulka, J
影响因子：
30.8
作者：
Jones, PL;Veenstra, GJC;Wolffe, AP
通讯作者：
Wolffe, AP