XIST Derepression in Active X Chromosome Hinders Pig Somatic Cell Nuclear Transfer

Publication date: Available online 11 January 2018 Source:Stem Cell Reports Author(s): Degong Ruan, Jiangyun Peng, Xiaoshan Wang, Zhen Ouyang, Qingjian Zou, Yi Yang, Fangbing Chen, Weikai Ge, Han Wu, Zhaoming Liu, Yu Zhao, Bentian Zhao, Quanjun Zhang, Chengdan Lai, Nana Fan, Zhiwei Zhou, Qishuai Liu, Nan Li, Qin Jin, Hui Shi, Jingke Xie, Hong Song, Xiaoyu Yang, Jiekai Chen, Kepin Wang, Xiaoping Li, Liangxue Lai 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 e...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research