Title: Overcoming Intrinsic H3K27me3 Imprinting Barriers Improves Post-implantation Development after Somatic Cell Nuclear Transfer
Author: Le-Yun Wang, Zhi-Kun Li, Li-Bin Wang, Chao Liu, Xue-Han Sun, Gui-Hai Feng, Jia-Qiang Wang, Yu-Fei Li, Lian-Yong Qiao, Hu Nie, Li-Yuan Jiang, Hao Sun, Ya-Li Xie, Si-Nan Ma, Hai-Feng Wan, Fa-Long Lu, Wei Li, Qi Zhou
Abstract: Successful cloning by somatic cell nuclear transfer (SCNT) requires overcoming significantepigenetic barriers. Genomic imprinting is not generally regarded as such a barrier,although H3K27me3-dependent imprinting is differentially distributed in E6.5 epiblastand extraembryonic tissues. Here we report significant enhancement of SCNT efficiencyby deriving somatic donor cells carrying simultaneous monoallelic deletion of fourH3K27me3-imprinted genes from haploid mouse embryonic stem cells. Quadruple monoallelicdeletion of Sfmbt2, Jade1, Gab1, and Smoc1 normalized H3K27me3-imprinted expression patterns and increased fibroblast cloningefficiency to 14% compared with a 0% birth rate from wild-type fibroblasts while preventingthe placental and body overgrowth defects frequently observed in cloned animals. Sfmbt2 deletion was the most effective of the four individual gene deletions in improvingSCNT. These results show that lack of H3K27me3 imprinting in somatic cells is an epigeneticbarrier that impedes post-implantation development of SCNT embryos and can be overcomeby monoallelic imprinting gene deletions in donor cells.
Cell Stem Cell：《细胞—干细胞》，创刊于2007年。隶属于细胞出版社，最新IF：21.464