Activation of paternally expressed imprinted genes in newly derived germline-competent mouse parthenogenetic embryonic stem cell lines  

作　　者：Hua Jiang Bowen Sun Weicheng Wang Zhihong Zhang Furong Gao Guilai Shi Bing Cui XiangyinKong Zhao He Xiaoyan Ding Ying Kuang Jian Fei Yi Juan Sun Yun Feng Ying Jin 

机构地区：[1]The Kev Laboratory of Stem Cell Biology, Institute of Health Sciences. Shanghai Institutes for Biological Sciences. Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, 225 South Chongqing Rd, Shanghai 200025, China [2]Shanghai Institute of Stem Cell Research, Shanghai JiaoTong University School of Medicine, 280 South Chongqing Rd, Shanghai 200025, China [3]Graduate School of Chinese Academy of Sciences, Beijing, China [4]Institute of Biochemical and Cellular Biologv, Shanghai Institutes.for Biological Sciences, Chinese Academv of Sciences, 320 Yueyang Rd, Shanghai 200031, China [5]Shanghai Research Center for Model Organisms, 88 Cai Lun Road, Shanghai 201203, China [6]Reproductive Medical Center, Ruijin Hospital, 197 Second Ruijin Rd, Shanghai 20135, China

出　　处：《Cell Research》2007年第9期792-803,共12页细胞研究（英文版）

摘　　要：Parthenogenetic embryonic stem （pES） cells provide a valuable in vitro model system for studying the molecular mechanisms that underlie genomic imprinting. However, the pluripotency of pES cells and the expression profiles of paternally expressed imprinted genes have not been fully explored. In this study, three mouse pES cell lines were established and the differentiation potential of these cells in extended culture was evaluated. The undifferentiated cells had a normal karyotype and homozygous genome, and expressed ES-cell-specific molecular markers. The cells remained undifferentiated after more than 50 passages and exhibited pluripotent differentiation capacity. All three lines of the established ES cells produced teratomas; two lines of ES cells produced chimeras and germline transmission. Furthermore, activation of the paternally expressed imprinted genes Snrpn, U2afl-rsl, Peg3, Impact, Zfp127, Dlkl and Mest in these cells was detected. Some paternally expressed imprinted genes were found to be expressed in the blastocyst stage of parthenogenetically activated embryos in vitro and their expression level increased with extended pES cell culture. Furthermore, our data show that the activation of these paternally expressed imprinted genes in pES cells was associated with a change in the methylation of the related differentially methylated regions. These findings provide direct evidence for the pluripotency of pES cells and demonstrate the association between the DNA methylation pattern and the activa- tion of paternally expressed imprinted genes in pES cells. Thus, the established ES cell lines provide a valuable model for studying epigenetic regulation in mammalian development.

关 键 词：PARTHENOGENESIS embryonic stem cell PLURIPOTENCY imprinted gene methylation 

分 类 号：R-332[医药卫生]