Adult mice cloned from migrating primordial germ cells

Yamazaki, Yukiko; Low, Eleanor W.; Marikawa, Yusuke; Iwahashi, Kazuhiro; Bartolomei, Marisa S.; McCarrey, John R.; Yanagimachi, Ryuzo

doi:10.1073/pnas.0504943102

Cited by 49 publications

(30 citation statements)

References 39 publications

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“…Several polymorphisms have been described that distinguish B6 and CAST alleles of imprinted genes on chromosome 7 [27,28]. Female B6/CAST mice were mated with male Tg OG2 mice to produce (B6/CAST 3 OG2) F1 hybrid fetuses [29]. GFP-positive germ cells were collected from these F1 fetuses to perform all experiments.…”

Section: Micementioning

confidence: 99%

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Autonomous Regulation of Sex-Specific Developmental Programming in Mouse Fetal Germ Cells1

Iwahashi

Yoshioka

Low

et al. 2007

Biology of Reproduction

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In mice, unique events regulating epigenetic programming (e.g., genomic imprinting) and replication state (mitosis versus meiosis) occur during fetal germ cell development. To determine whether these processes are autonomously programmed in fetal germ cells or are dependent upon ongoing instructive interactions with surrounding gonadal somatic cells, we isolated male and female germ cells at 13.5 days postcoitum (dpc) and maintained them in culture for 6 days, either alone or in the presence of feeder cells or gonadal somatic cells. We examined allele-specific DNA methylation in the imprinted H19 and Snrpn genes, and we also determined whether these cells remained mitotic or entered meiosis. Our results show that isolated male germ cells are able to establish a characteristic "paternal" methylation pattern at imprinted genes in the absence of any support from somatic cells. On the other hand, cultured female germ cells maintain a hypomethylated status at these loci, characteristic of the normal "maternal" methylation pattern in endogenous female germ cells before birth. Further, the surviving female germ cells entered first meiotic prophase and reached the pachytene stage, whereas male germ cells entered mitotic arrest. These results indicate that mechanisms controlling both epigenetic programming and replication state are autonomously regulated in fetal germ cells that have been exposed to the genital ridge prior to 13.5 dpc.

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Section: Micementioning

confidence: 99%

“…One set of genomic DNA prepared from 120-200 GFP-positive germ cells was used for one PCR amplification [29]. For endogenous control and cultured female germ cells, one to two sets of genomic DNA were prepared for each stage.…”

Section: Bisulfite Genomic Sequencingmentioning

confidence: 99%

Autonomous Regulation of Sex-Specific Developmental Programming in Mouse Fetal Germ Cells1

Iwahashi

Yoshioka

Low

et al. 2007

Biology of Reproduction

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“…This epigenetic plasticity is essential to the process of germ cell sex differentiation, and the acquisition of developmental competence by both the sperm and the oocyte genomes [19]. Nuclear transfer (cloning) has been used to assess the correlation of epigenetic plasticity and developmental potential of fetal germ cell genomes [20][21][22][23][24]. We and others found that germ cell nuclei taken from fetuses at 8.5-10.5 dpc were fully competent to support development of viable cloned offspring based on inherited epigenetic programming that had not yet been erased [23,24], whereas germ cell nuclei recovered at 11.5 dpc or later were developmentally incompetent [20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…Nuclear transfer (cloning) has been used to assess the correlation of epigenetic plasticity and developmental potential of fetal germ cell genomes [20][21][22][23][24]. We and others found that germ cell nuclei taken from fetuses at 8.5-10.5 dpc were fully competent to support development of viable cloned offspring based on inherited epigenetic programming that had not yet been erased [23,24], whereas germ cell nuclei recovered at 11.5 dpc or later were developmentally incompetent [20][21][22]. This loss of developmental competence was correlated with the initial erasure, and subsequent biallelic resetting of genomic imprints in the germline genomes in both sexes, resulting in identical imprinting (or lack thereof) on both alleles of each imprinted gene in these cells.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Nuclear Organization of Constitutive Heterochromatin During Fetal Male Germ Cell Development in Mice1

Yoshioka

McCarrey

Yamazaki

2009

Biology of Reproduction

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In mice, male germ cells enter mitotic arrest beginning at 13.5 days postcoitum (dpc), and remain suspended in the G(0)/G(1) cell cycle stage until after birth. During this period, male germ cells undergo extensive epigenetic reprogramming, which is essential for their subsequent function as male gametes. A global reorganization and spatial clustering of constitutive heterochromatin has been implicated in epigenetic plasticity during cellular differentiation. Here, we have studied the dynamics of heterochromatin in fetal (12.5-19.5 dpc) and neonatal (4 days postpartum) male germ cells. We monitored constitutive heterochromatin-specific markers, and observed changes in the association of histone H3 trimethylation of lysine 9 (H3K9me3), binding of heterochromatin protein 1, and patterns of 4',6-diamino-2-phenylindole staining in pericentric regions of chromosomes, along with a coincident loss of chromocenters in fetal prospermatogonia during mitotic arrest. We also observed a transient loss of H3K9me3 associated with major and minor satellite repeat sequences, plus inactivation of histone methyltransferases (Suv39h1 and Suv39h2), and transient activation of histone demethylase (Jmjd2b) in these same cells. These epigenetic changes were correlated with relocation of centromeric regions toward the nuclear periphery in prospermatogonia during mitotic arrest. Taken together, these results show that constitutive heterochromatin undergoes dramatic reorganization during prespermatogenesis. We suggest that these dynamic changes in heterochromatin contribute to normal epigenetic reprogramming of the paternal genome in fetal prospermatogonia suspended in the G(0)/G(1) stage, and that this also represents an epigenomic state that is particularly amenable to reprogramming.

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“…It is still unclear whether all the epigenetic information is reset in the germ line. However, nuclear transfer using nuclei of PGCs before the demethylation wave resulted in viable mice, whereas nuclear transfer with nuclei of demethylated PGCs resulted in embryonic lethality [19,20]. Female ES cells show global genome hypomethylation, similar to the methylation status of the inner cell mass and this is in part due to the presence of two active X chromosomes [21].…”

Section: Methylating the Dnamentioning

confidence: 99%

Of Stem Cells and Gametes: Similarities and Differences

Lopes

2008

CMC

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Fusion of a mammalian sperm cell with an oocyte will lead to the formation of a new organism. As this new organism develops, the cells that construct the organism gradually lose developmental competence and become differentiated, a process which is in part mediated via epigenetic modifications. These mechanisms include DNA methylation, histone tail modifications and association with Polycomb and Trithorax proteins. Several cells within the organism must however maintain or regain developmental competence while they are highly specialized. These are the primordial germ cells that form the gametes; the oocytes and sperm cells. In this review different epigenetic modifying mechanisms will be discussed as they occur in developing embryos. In addition, aspects of nuclear reprogramming that are likely to occur via removal of epigenetic modifications are important, and several epigenetic removal mechanisms are indeed also active in developing germ cells.In vivo, a pluripotent cell has the capacity to form gametes, but in vitro terminal gametogenesis has proven to be difficult. Although development of pluripotent cells to cells with the characteristics of early germ cells has been unequivocally demonstrated, creating the correct culture milieu that enables further maturation of these cells has as yet been futile. Keywords:Embryo, primordial germ cell, epigenetics, pluripotency, ES cell, methylation. CELLULAR POTENCYAfter an oocyte has fused with a sperm cell, a new organism will be formed. During the development of this organism, the cells that construct the embryo will gradually lose developmental potential and gain more specialized functions. In this respect, differentiation equals a loss in cellular potency. One group of cells however has to maintain the capacity to form a new organism. This group encompasses the primordial germ cells (PGCs) that will give rise to the gametes later in development. Germ cells are unique cells since they are responsible for the continuity of genetic information across generations. They therefore have to maintain a certain level of cellular potency. In vertebrates, PGCs belong to the first embryonic lineage to be segregated, long before the gonads are recognizable. This specification event occurs outside the embryo at the border between the extraembryonic and embryonic region so that the PGCs can escape differentiation signals. Thereafter, the PGCs follow a complex migratory pattern to finally colonize the gonads [1].Once in the gonads, male PGCs enter mitotic arrest (prespermatogonia cells) whereas female PGCs enter meiosis (oogonia). In males, the pre-spermatogonia cells start proliferating only after birth and give rise to spermatogonia which either self-renew or differentiate to cells that enter meiosis forming haploid sperm cells. Spermatogonia are therefore considered an adult stem cell population. The oogonia, on the other hand, undergo meiosis synchronously during embryonic development and arrest in the diplotene stage at birth. After puberty, oocytes periodically matu...

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Adult mice cloned from migrating primordial germ cells

Cited by 49 publications

References 39 publications

Autonomous Regulation of Sex-Specific Developmental Programming in Mouse Fetal Germ Cells1

Autonomous Regulation of Sex-Specific Developmental Programming in Mouse Fetal Germ Cells1

Dynamic Nuclear Organization of Constitutive Heterochromatin During Fetal Male Germ Cell Development in Mice1

Of Stem Cells and Gametes: Similarities and Differences

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