Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term

Wu, Qiong; Kumagai, Takuya; Kawahara, Manabu; Ogawa, Hidehiko; Hiura, Hitoshi; Obata, Yayoi; Takano, Ryosuke; Kono, Toru

doi:10.1530/rep.1.00933

Cited by 46 publications

(33 citation statements)

References 23 publications

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“…Kono and co-workers showed that a 13 kb deletion encompassing the H19 coding region and the upstream differentially methylated region (DMR) allows parthenogenetic embryos to develop to term [22]. The efficiency of full-term development significantly increases when the H19/Igf2 DMR together with the DMR found within a second imprinted gene cluster Dlk1/Dio3 on chromosome 12 are deleted [23,32]. Most recently Hikichi et al showed that the development of PG embryos can be extended following serial nuclear transfer (NT) and is associated with a decrease in H19 expression [33].…”

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confidence: 99%

Downregulation ofH19Improves the Differentiation Potential of Mouse Parthenogenetic Embryonic Stem Cells

Ragina

Schlosser

Knott

et al. 2012

Stem Cells and Development

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Parthenogenetic embryonic stem cells (P-ESCs) offer an alternative source of pluripotent cells, which hold great promise for autologous transplantation and regenerative medicine. P-ESCs have been successfully derived from blastocysts of several mammalian species. However, compared with biparental embryonic stem cells (B-ESCs), P-ESCs are limited in their ability to fully differentiate into all 3 germ layers. For example, it has been observed that there is a differentiation bias toward ectoderm derivatives at the expense of endoderm and mesoderm derivatives-muscle in particular-in chimeric embryos, teratomas, and embryoid bodies. In the present study we found that H19 expression was highly upregulated in P-ESCs with more than 6-fold overexpression compared with B-ESCs. Thus, we hypothesized that manipulation of the H19 gene in P-ESCs would alleviate their limitations and allow them to function like B-ESCs. To test this hypothesis we employed a small hairpin RNA approach to reduce the amount of H19 transcripts in mouse P-ESCs. We found that downregulation of H19 led to an increase of mesoderm-derived muscle and endoderm in P-ESCs teratomas similar to that observed in B-ESCs teratomas. This phenomenon coincided with upregulation of mesoderm-specific genes such as Myf5, Myf6, and MyoD. Moreover, H19 downregulated P-ESCs differentiated into a higher percentage of beating cardiomyocytes compared with control P-ESCs. Collectively, these results suggest that P-ESCs are amenable to molecular modifications that bring them functionally closer to true ESCs.

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confidence: 99%

Downregulation ofH19Improves the Differentiation Potential of Mouse Parthenogenetic Embryonic Stem Cells

Ragina

Schlosser

Knott

et al. 2012

Stem Cells and Development

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“…We carried out further methylation analysis of the IG-DMR of Dlk1-Gtl2 in survivor ng Δch7 /fg BMEs. Interestingly, we observed a higher frequency of hypermethylated patterns in the ng Δch7 allele and partial methylation in the fg allele [21]. The reason for the different IG-DMR methylation patterns of Dlk1 in the ng Δch7 /fg BMEs is unknown.…”

Section: Riddle Arising From Birth Of "Kaguya"mentioning

confidence: 70%

Roles of Genes Regulated by Two Paternally Methylated Imprinted Regions on Chromosomes 7 and 12 in Mouse Ontogeny

Kawahara

Kono

2012

Journal of Reproduction and Development

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Abstract. We studied the longevity of mice produced without sperm using the genomes of oocytes that are already committed to a germline cell lineage. The first sperm-free mouse "KAGUYA", which we term 'bi-maternal mouse', was born on 3 February, 2003. Bi-maternal embryos were generated using 2 sets of female genomes-one derived from fully grown oocytes from normal adults and the other from non-growing oocytes from newborn pups. These genomes were combined by nuclear transfer. We refined the technique for generating bi-maternal mice and found that genetic manipulations in only 2 regions-the imprinting centres of Igf2-H19 and Dlk1-Gtl2-on chromosomes 7 and 12 of the newborn pups allowed us to generate bi-maternal mice at a high rate. Studying bi-maternal conceptuses and mice provides further insight into the mechanisms by which paternally methylated imprinted genes regulate mammalian ontogenesis. Key words: Development, Dlk1, Genomic imprinting, Gtl2, H19, Igf2, Mouse (J. Reprod. Dev. 58: [175][176][177][178][179] 2012) A ndrogenetic and parthenogenetic embryos fail to develop past early post-implantation and mid-gestation respectively, and disruption of imprinting is implicated in serious human diseases such as Angelman syndrome, Prader-Willi syndrome, BeckwithWiedemann syndrome, and Silver-Russell syndrome [1][2][3]. However, parthenogenesis is not unusual for non-mammals. For instance, parthenogenesis in turkey was studied for many years, and in fact, as many as 1 to 30% of unfertilized turkey eggs develop embryos [4][5][6][7][8][9]. In mammals, full development typically requires genomes from both the oocyte and spermatozoon. Previous studies have revealed that embryos possessing two paternally derived pronuclei (androgenones) or two maternally derived pronuclei (gynogenones and parthenogenones) fail to develop to term [10][11][12]. In mammals, imprinted genes, wherein only one of the two parental chromosome copies is expressed, are regulated by epigenetic modifications, including DNA methylation [13]. Genomic imprinting regulates the expression of developmentally crucial mammalian genes. How can the function of the germ line-specific methylation imprints during embryo development be elucidated? It is impossible to directly assess the genome competence of non-growing (ng) and growing-stage oocytes to support development. This is because at these stages, the oocytes are entirely incompetent and are unable to mature to the metaphase of the second meiosis (MII), undergo fertilization and develop.We established serial nuclear transfer as a reliable procedure for reconstructing oocytes containing two haploid sets of maternal genomes by using oocytes obtained from different sources [14][15][16][17].In the first nuclear transfer, an ng oocyte from growing stage oocytes was fused with a fully grown germinal vesicle (GV)-stage (GV-fg) oocyte from which the GV was previously removed. In the second nuclear transfer, the resultant MII spindle derived from the ng oocyte was transferred into an intact MII oocyte. Followi...

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“…Fetal development is promoted generally by paternally expressed genes (Wu et al, 2006), whereas maternally expressed genes have a tendency to restrict fetal growth (Abu-Amero et al, 2008). Imprinting is found predominantly in placental mammals, and may participate in the balance of parental resource allocation to the offspring (Ishida and Moore, 2013).…”

Section: Introductionmentioning

confidence: 99%

MetaImprint: an information repository of mammalian imprinted genes

Wei

Liu

et al. 2014

Development

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Genomic imprinting is a complex genetic and epigenetic phenomenon that plays important roles in mammalian development and diseases. Mammalian imprinted genes have been identified widely by experimental strategies or predicted using computational methods. Systematic information for these genes would be necessary for the identification of novel imprinted genes and the analysis of their regulatory mechanisms and functions. Here, a well-designed information repository, MetaImprint (http://bioinfo.hrbmu.edu.cn/ MetaImprint), is presented, which focuses on the collection of information concerning mammalian imprinted genes. The current version of MetaImprint incorporates 539 imprinted genes, including 255 experimentally confirmed genes, and their detailed research courses from eight mammalian species. MetaImprint also hosts genome-wide genetic and epigenetic information of imprinted genes, including imprinting control regions, single nucleotide polymorphisms, non-coding RNAs, DNA methylation and histone modifications. Information related to human diseases and functional annotation was also integrated into MetaImprint. To facilitate data extraction, MetaImprint supports multiple search options, such as by gene ID and disease name. Moreover, a configurable Imprinted Gene Browser was developed to visualize the information on imprinted genes in a genomic context. In addition, an Epigenetic Changes Analysis Tool is provided for online analysis of DNA methylation and histone modification differences of imprinted genes among multiple tissues and cell types. MetaImprint provides a comprehensive information repository of imprinted genes, allowing researchers to investigate systematically the genetic and epigenetic regulatory mechanisms of imprinted genes and their functions in development and diseases.

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Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term

Cited by 46 publications

References 23 publications

Downregulation ofH19Improves the Differentiation Potential of Mouse Parthenogenetic Embryonic Stem Cells

Downregulation ofH19Improves the Differentiation Potential of Mouse Parthenogenetic Embryonic Stem Cells

Roles of Genes Regulated by Two Paternally Methylated Imprinted Regions on Chromosomes 7 and 12 in Mouse Ontogeny

MetaImprint: an information repository of mammalian imprinted genes

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