Activation of paternally expressed imprinted genes in newly derived germline-competent mouse parthenogenetic embryonic stem cell lines.
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, U2af1-rs1, Peg3, Impact, Zfp127, Dlk1 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 activation 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.
Jiang
Hua
H
The Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai JiaoTong University School of Medicine, Shanghai, China.
Sun
Bowen
B
Wang
Weicheng
W
Zhang
Zhihong
Z
Gao
Furong
F
Shi
Guilai
G
Cui
Bing
B
Kong
Xiangyin
X
He
Zhao
Z
Ding
Xiaoyan
X
Kuang
Ying
Y
Fei
Jian
J
Sun
Yi Juan
YJ
Feng
Yun
Y
Jin
Ying
Y
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D002678:Chimera / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000502:physiology*