Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development.
Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development.
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DOI：
10.1016/j.stem.2018.06.008
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发表时间：
2018-09-06
期刊：
影响因子：
23.9
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Matoba S;Wang H;Jiang L;Lu F;Iwabuchi KA;Wu X;Inoue K;Yang L;Press W;Lee JT;Ogura A;Shen L;Zhang Y
动物克隆可以通过体细胞核移植（SCNT）来实现，尽管活产率相对较低。最近的研究发现，供体细胞中的H3K9me3和异常的Xist激活是阻碍SCNT的表观遗传屏障。在这里，我们利用敲除Xist的供体细胞和过表达Kdm4的组合克服了这些障碍，实现了超过20%的小鼠SCNT效率。然而，植入后缺陷和胎盘异常仍然存在，这表明有额外的表观遗传障碍阻碍了SCNT的克隆。体外受精和SCNT囊胚的DNA甲基组比较分析发现，尽管成功地进行了甲基组重编程，但SCNT胚胎中存在异常甲基化区域。引人注目的是，植入前SCNT胚胎的等位基因转录组学和ChIP-seq分析显示H3K27me3印迹完全缺失，这可能解释了SCNT胚胎中观察到的出生后发育缺陷。总之，这些结果为小鼠克隆提供了一种有效的方法，同时为进一步提高SCNT的效率铺平了道路。Matoba等研究表明，通过同时克服Xist和H3K9me3两个重编程障碍，可以显著提高小鼠克隆效率，尽管与IVF相比效率仍然较低。综合分析表明，SCNT胚胎可以完全丧失H3K27me3印迹，这可能解释了这种低效率。
Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), although the live birth rate is relatively low. Recent studies have identified H3K9me3 in donor cells and abnormal Xist activation as epigenetic barriers that impede SCNT. Here we overcome these barriers using a combination of Xist knockout donor cells and overexpression of Kdm4 to achieve more than 20% efficiency of mouse SCNT. However, post-implantation defects and abnormal placentas were still observed, indicating that additional epigenetic barriers impede SCNT cloning. Comparative DNA methylome analysis of IVF and SCNT blastocysts identified abnormally methylated regions in SCNT embryos despite successful global reprogramming of the methylome. Strikingly, allelic transcriptomic and ChIP-seq analyses of pre-implantation SCNT embryos revealed complete loss of H3K27me3 imprinting, which may account for the postnatal developmental defects observed in SCNT embryos. Together, these results provide an efficient method for mouse cloning while paving the way for further improving SCNT efficiency. Matoba et al. show that mouse cloning efficiency can be significantly improved by simultaneously overcoming two reprogramming barriers, Xist and H3K9me3, although efficiency is still low in comparison with IVF. Comprehensive analyses showed that SCNT embryos can have complete loss of H3K27me3 imprinting, likely explaining this low efficiency.
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DOI：
10.1126/science.1229277
发表时间：
2013-01-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hackett JA;Sengupta R;Zylicz JJ;Murakami K;Lee C;Down TA;Surani MA
通讯作者：
Surani MA
影响因子：
3.8
作者：
Ao, Zheng;Liu, Dewu;Wu, Zhenfang
通讯作者：
Wu, Zhenfang
影响因子：
4.5
作者：
Kobayashi H;Sakurai T;Imai M;Takahashi N;Fukuda A;Yayoi O;Sato S;Nakabayashi K;Hata K;Sotomaru Y;Suzuki Y;Kono T
通讯作者：
Kono T
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
11.8
作者：
Branco MR;King M;Perez-Garcia V;Bogutz AB;Caley M;Fineberg E;Lefebvre L;Cook SJ;Dean W;Hemberger M;Reik W
通讯作者：
Reik W