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

Jiang, Hua; Sun, Bowen; Wang, Weicheng; Zhang, Zhihong; Gao, Furong; Shi, Guang; Cui, Bing; Kong, Xiangyin; He, Zhao; Ding, Xiaoyan; Kuang, Ying; Fei, Jian; Sun, Yi; Feng, Yun; Jin, Ying

doi:10.1038/cr.2007.70

Cited by 38 publications

(42 citation statements)

References 34 publications

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“…Although with decreased numbers, these Nanog þ /Sox2 þ epiblast cells still exist in the parthenote ICM and can be used to derive patient-specific ES cells for stem cell therapies. On the other hand, there are other drawbacks of parthenogenetic embryos, which had been previously reported, including aberrant expression of imprinted and development-related genes that disrupt full development of organisms (Humpherys et al, 2001;Zvetkova et al, 2005;Bonk et al, 2007;Jiang et al, 2007;Mitalipov et al, 2007;Horii et al, 2008). Our study showed the abnormal gene expression in the preimplantation parthenogenetic embryo, which Fig.…”

Section: Discussionmentioning

confidence: 49%

Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos

Chen

2012

Developmental Dynamics

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Background: Parthenogenetic mammalian embryos were reported to die in utero no later than the 25-somite stage due to abnormal development of both embryonic and extraembryonic lineages. Interestingly, it has been shown that parthenogenetic ICM cells tend to differentiate more into primitive endoderm cells and less into epiblast and ES cells. Hence we are interested in studying the molecular mechanisms underlying lineage defects of parthenotes. Results: We found that parthenote inner cell masses (ICMs) contained decreased numbers of Sox2 1 /Nanog 1 epiblast cells but increased numbers of Gata4 1 primitive endoderm cells, indicating an unusual lineage segregation. We demonstrate for the first time that the increased Gata4 level in parthenotes may be explained by the strong up-regulation of Fgf3 and Fgfr2 phosphorylation. Inhibition of Fgfr2 activation by SU5402 in parthenotes restored normal Nanog and Gata4 levels without affecting Fgf3, indicating that Fgf3 is upstream of Fgfr2 activation. In parthenote trophectoderm, we detected normal Cdx2 but ectopic Gata4 expression and reduced Elf5 and Tbr2(Eomes) levels. Conclusions: Taken together, our work provides for the first time the insight into the molecular mechanisms of the developmental defects of parthenogenetic embryos in both the trophectoderm and ICM.

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Section: Discussionmentioning

confidence: 49%

Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos

Chen

2012

Developmental Dynamics

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“…However, in this study, we found aberrant expression of some imprinted genes in FY-phES-018 cells. Although altered expression of paternally expressed imprinted genes has been reported recently in pmESC lines [17,18,39] and in a differentiated phESC line (chHES-32) [4], the mechanism of imprinting changes in phESCs is not fully understood. Thus, phESCs could be a useful model for studying the mechanisms of epigenetic regulation and imprinting.…”

Section: Discussionmentioning

confidence: 99%

Genetic and epigenetic X-chromosome variations in a parthenogenetic human embryonic stem cell line

Liu

Yin

Jiang

et al. 2010

J Assist Reprod Genet

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Purpose To assess the genetic and epigenetic status of parthenogenetic human embryonic stem cells (phESCs). Methods Cytogenetics, X chromosome inactivation (XCI) and gene expression patterns were analyzed in one phESC line (FY-phES-018) that was derived from our laboratory. Results FY-phES-018 cells displayed the classical characteristics of normal hESCs. These cells had a 46, XX karyotype, and no inactive X chromosomes were observed before passage 20. After being cultured long term in vitro, some cells lost one X, and the proportion of cells with only one X gradually increased. At passage 35, almost all the cells displayed a 45, XO karyotype. Interestingly, at passage 45, the recovery of the X-chromosome was observed, and XCI became detectable; the mosaic ratio of 46, XX to 45, XO was 67:33. After passage 60, most cells displayed the 46, XX karyotype again with a mosaic ratio of 97:3. Some aberrant genomic imprinting was also observed in these cells. Conclusions The phESCs line FY-phES-018 is both genetically and epigenetically unstable; therefore, further research is needed before using these cells.

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“…Most of the chimeras from aES cells had skeletal abnormality and other defects [10,23], and no chimeras were generated from two mature sperms derived aES cells assisted with SCNT previously. Some labs tried to erase the strict imprinting of uniparental ES cells by serial nuclear transfer method [24] or long-term cell culture [25]. But these methods were either complicated or time-consuming.…”

Section: Discussionmentioning

confidence: 99%

Derivation of androgenetic embryonic stem cells from m-carboxycinnamic acid bishydroxamide (CBHA) treated androgenetic embryos

et al. 2013

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The androgenetic embyronic stem (aES) cells are useful models in studying the effects of imprinted genes on pluripotency maintaining and embryo development. The expression patterns of imprinted genes are significantly different between uniparental derived aES cells and zygote-derived embryonic stem (ES) cells, therefore, the imprinting related cell pluripotency needs further exploitation. Several approaches have been applied in generation of androgenetic embryos and derivation of aES cell lines. Here, we describe a method to generate androgenetic embryos by injecting two mature sperms into one enucleated oocyte. Then these androgenetic embryos were treated with a histone deacetylase inhibitor: m-carboxycinnamic acid bishydroxamide (CBHA). Further, aES cell lines were successfully derived from these treated androgenetic embryos at blastocyst stage. The CBHA could improve not only the quality of androgenetic embryos, but also the efficiencies of aES (CaES) cells derivation and chimeric mice generation. The imprinted gene expression pattern in the CBHA treated embryo-derived aES (CaES) cells was also highly similar to that of zygote-derived ES cells. CBHA, androgenetic, aES, pluripotency Citation:Shuai L, Feng C J, Zhang H J, et al. Derivation of androgenetic embryonic stem cells from m-carboxycinnamic acid bishydroxamide (CBHA) treated androgenetic embryos.

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

Cited by 38 publications

References 34 publications

Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos

Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos

Genetic and epigenetic X-chromosome variations in a parthenogenetic human embryonic stem cell line

Derivation of androgenetic embryonic stem cells from m-carboxycinnamic acid bishydroxamide (CBHA) treated androgenetic embryos

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