XIST Derepression in Active X Chromosome Hinders Pig Somatic Cell Nuclear Transfer.
XIST Derepression in Active X Chromosome Hinders Pig Somatic Cell Nuclear Transfer.
复制标题
活性 X 染色体中的 XIST 去抑制阻碍猪体细胞核移植
DOI：
10.1016/j.stemcr.2017.12.015
复制
发表时间：
2018-02-13
影响因子：
5.9
通讯作者：
Lai L
中科院分区：
文献类型：
--
作者：
Ruan D;Peng J;Wang X;Ouyang Z;Zou Q;Yang Y;Chen F;Ge W;Wu H;Liu Z;Zhao Y;Zhao B;Zhang Q;Lai C;Fan N;Zhou Z;Liu Q;Li N;Jin Q;Shi H;Xie J;Song H;Yang X;Chen J;Wang K;Li X;Lai L
通过体细胞核移植（SCNT）克隆猪的效率仍然极低，许多克隆胚胎发育异常。在这里，通过分析转录组表达，我们观察到在每条染色体中染色体范围内的基因表达失调，并确定了相当数量的基因在异常克隆胚胎中异常表达。特别是，XIST，一个长的非编码RNA基因，在异常胚胎中表现出高异位表达。我们还证明，供体细胞中XIST基因的缺失可以使克隆胚胎中异常的基因表达正常化，并增强胚胎的长期发育能力。此外，XIST缺陷胚胎质量的提高与H3K9me3的整体减少有关。向NT胚胎注射H3K9me去甲基化酶Kdm4A可促进附植前期胚胎的发育。然而，Kdm4A除了也诱导XIST去阻遏在活跃的X染色体，因此是不能够提高在体内的长期发育能力的猪NT胚胎。正常和异常猪SCNT胚胎的转录组模式不同，破坏供体细胞中的XIST基因可以提高猪NT胚胎的发育能力，注射Kdm 4A可以提高猪植入前胚胎的发育能力，Kdm 4A的加入导致XIST去抑制，不能提高猪克隆效率。Liangxue Lai及其同事表明，供体细胞中XIST基因的缺失可以使克隆胚胎中异常的基因表达正常化，从而提高猪的克隆效率。
Pig cloning by somatic cell nuclear transfer (SCNT) remains extremely inefficient, and many cloned embryos undergo abnormal development. Here, by profiling transcriptome expression, we observed dysregulated chromosome-wide gene expression in every chromosome and identified a considerable number of genes that are aberrantly expressed in the abnormal cloned embryos. In particular, XIST, a long non-coding RNA gene, showed high ectopic expression in abnormal embryos. We also proved that nullification of the XIST gene in donor cells can normalize aberrant gene expression in cloned embryos and enhance long-term development capacity of the embryos. Furthermore, the increased quality of XIST-deficient embryos was associated with the global H3K9me3 reduction. Injection of H3K9me demethylase Kdm4A into NT embryos could improve the development of pre-implantation stage embryos. However, Kdm4A addition also induced XIST derepression in the active X chromosome and thus was not able to enhance the in vivo long-term developmental capacity of porcine NT embryos. Normal and abnormal pig SCNT embryos featured different transcriptome patterns Disrupting XIST gene in donor cells could enhance pig NT embryo development capacity Kdm4A injection was able to improve development of pig pre-implantation stage embryos Kdm4A addition caused XIST derepression and failed to improve pig cloning efficiency In this article, Liangxue Lai and colleagues show that nullification of the XIST gene in donor cells can normalize aberrant gene expression in cloned embryos and result in high cloning efficiency in pigs.
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DOI：
10.1262/jrd.2012-195
发表时间：
2013
期刊：
The Journal of reproduction and development
影响因子：
--
作者：
Oikawa M;Matoba S;Inoue K;Kamimura S;Hirose M;Ogonuki N;Shiura H;Sugimoto M;Abe K;Ishino F;Ogura A
通讯作者：
Ogura A
影响因子：
4.4
作者：
Cao S;Han J;Wu J;Li Q;Liu S;Zhang W;Pei Y;Ruan X;Liu Z;Wang X;Lim B;Li N
通讯作者：
Li N
影响因子：
3.7
作者：
Diao YF;Oqani RK;Li XX;Lin T;Kang JW;Jin DI
通讯作者：
Jin DI
影响因子：
1.9
作者：
Park, Ki-Eun;Johnson, Christine M.;Cabot, Ryan A.
通讯作者：
Cabot, Ryan A.
影响因子：
14.9
作者：
Amarzguioui, M;Holen, T;Prydz, H
通讯作者：
Prydz, H