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2. Heterogeneity in imprinted methylation patterns of pluripotent embryonic germ cells derived from pre-migratory mouse germ cells

Author

Shovlin, Tanya C., Durcova-Hills, Gabriela, Surani, Azim, and McLaren, Anne

Subjects
Biological sciences
Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2007.11.007 Byline: Tanya C. Shovlin, Gabriela Durcova-Hills, Azim Surani, Anne McLaren Keywords: Embryonic germ (EG) cells; Primordial germ cells (PGCs); Embryonic stem (ES) cells; DNA methylation; Germ cell development Abstract: Pluripotent stem cells, termed embryonic germ (EG) cells, have been generated from both human and mouse primordial germ cells (PGCs). Like embryonic stem (ES) cells, EG cells have the potential to differentiate into all germ layer derivatives and may also be important for any future clinical applications. The development of PGCs in vivo is accompanied by major epigenetic changes including DNA demethylation and imprint erasure. We have investigated the DNA methylation pattern of several imprinted genes and repetitive elements in mouse EG cell lines before and after differentiation. Analysed cell lines were derived soon after PGC specification, 'early', in comparison with EG cells derived after PGC colonisation of the genital ridge, 'late' and embryonic stem (ES) cell lines, derived from the inner cell mass (ICM). Early EG cell lines showed strikingly heterogeneous DNA methylation patterns, in contrast to the uniformity of methylation pattern seen in somatic cells (control), late EG cell and ES cell lines. We also observed that all analysed XX cell lines exhibited less methylation than XY. We suggest that this heterogeneity may reflect the changes in DNA methylation taking place in the germ cell lineage soon after specification. Author Affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QN, UK Article History: Received 3 September 2007; Revised 25 October 2007; Accepted 2 November 2007

Published
2008

3. Analysis of sex differences in EGC imprinting

Author

Durcova-Hills, Gabriela, Burgoyne, Paul, and McLaren, Anne

Subjects
Stem cells -- Research, Biological sciences
Abstract

Sex-specific differences are apparent in the methylation patterns of H19 and Igf2 imprinted genes in embryonic germ cells (EGCs) derived from 11.5 or 12.5 days post coitum (dpc) primordial germ cells (PGCs). Here we studied whether these differences are associated either with the sex chromosome constitution of the EGCs or with the sex of the genital ridge (testis versus ovary) from which the PGCs were isolated. For this purpose we derived pluripotent EGC lines from sex-reversed embryos, either XY embryos deleted for Sry (X[Y.sup.Tdym1]) or XX embryos carrying an Sry transgene. Southern blotting of the EGC DNA was used to analyze the differentially methylated regions of Igf2 and H19. The analysis revealed that both genes were more methylated in EGCs with an XY sex chromosome constitution than in those with an XX sex chromosome constitution, irrespective of the phenotypic sex of the genital ridge from which the EGCs had been derived. We conclude that the sex-specific methylation is intrinsic and cell-autonomous, and is not due to any influence of the genital ridge somatic cells upon the PGCs. Keywords: Imprinting; PGCs; Pluripotent stem cells; Igf2; H19; Sex-reversed

Published
2004

5. Contributors

Author

Addis, Russell C., primary, Alberts, Bruce, additional, Amit, Michal, additional, Andrews, Peter W., additional, Aoki, Hitomi, additional, Asashima, Makoto, additional, Axelman, Joyce, additional, Becker, Daniel, additional, Benvenisty, Nissim, additional, Bhatia, Mickie, additional, Blackburn, C. Clare, additional, Boiani, Michele, additional, Bonner-Weir, Susan, additional, Bowles, Josephine, additional, Boyd, Richard L., additional, Bronner-Fraser, Marianne, additional, Brunskill, Eric W., additional, Bultman, Scott, additional, Campbell, Frederick Charles, additional, Camus, Anne, additional, Carpenter, Melissa K., additional, Cavaleri, Fatima, additional, Cepko, Constance, additional, Chen, Yijing, additional, de Sousa Lopes, Susana M. Chuva, additional, Clark, Gregory O., additional, Collignon, Jérôme, additional, Collodi, Paul, additional, Cowan, Chad, additional, Daley, George Q., additional, Dani, Christian, additional, Dowell, Joshua D., additional, Draper, Jonathan S., additional, Dressler, Gregory R., additional, Drukker, Micha, additional, Durcova-Hills, Gabriela, additional, Edwards, Robert G., additional, Eisenberg, Rebecca S., additional, Elluru, Ravindhra, additional, Evans, Sir Martin, additional, Fan, Lianchun, additional, Farley, Margaret A., additional, Fekete, Donna M., additional, Field, Loren J., additional, Fink, Donald W., additional, Forrester, Lesley M., additional, Fuller, Margaret T., additional, Furue, Miho, additional, Garbers, David L., additional, Gardner, Richard L., additional, Gearhart, John D., additional, Gerecht-Nir, Sharon, additional, Gill, Jason W., additional, Gonzalez, Rodolfo, additional, Gray, Daniel H.D., additional, Green, Ronald M., additional, Gropp, Michal, additional, Haagensen, Alexandra, additional, Hamra, F. Kent, additional, Harvey, Richard P., additional, Hawes, Susan M., additional, Hayashi, Shin-Ichi, additional, Hazlehurst, Anne L., additional, Hemmi, Hiroaki, additional, Hisatsune, Hiroshi, additional, Huettner, James, additional, Huntsman, Bradley, additional, Iéhlé, Catherine, additional, Imitola, Jamie, additional, Itskovitz-Eldor, Joseph, additional, Jaenisch, Rudolf, additional, Johnson, Penny A., additional, Jones, D. Leanne, additional, Jones, Elizabeth A., additional, Karsenty, Gerard, additional, Katz, Gil, additional, Kaur, Pritinder, additional, Kelly, Robert G., additional, Kent, Kathleen C., additional, Kerr, Candace L., additional, Khademhosseini, Ali, additional, Khaner, Hanita, additional, Kintner, Chris, additional, Klimanskaya, Irina, additional, Kondoh, Nobuyuki, additional, Koopman, Peter, additional, Koyano-Nakagawa, Naoko, additional, Kraszewski, Jennifer N., additional, Krumlauf, Robb, additional, Kunath, Tilo, additional, Kunisada, Takahiro, additional, Langer, Robert, additional, Lanza, Robert, additional, Lee, Jean Pyo, additional, Levenberg, Shulamit, additional, Levine, S. Robert, additional, Lin, Haifan, additional, Littlefield, John W., additional, Lysaght, Michael J., additional, Mack, Fiona A., additional, Magnuson, Terry, additional, Malashicheva, Anna, additional, Mandelboim, Ofer, additional, Manley, Nancy R., additional, Matthaei, Klaus I., additional, Mayshar, Yoav, additional, McDonald, John W., additional, McLaren, Dame Anne, additional, McMahon, Jill, additional, Meissner, Alexander, additional, von Melchner, Harald, additional, Melton, Douglas A., additional, Montgomery, Nathan, additional, Moore, Mary Tyler, additional, Motohashi, Tsutomu, additional, Mueller, Franz-Josef, additional, Mummery, Christine, additional, Nishikawa, Satomi, additional, Nishikawa, Shin-Ichi, additional, Nagy, Andras, additional, Niwa, Hitoshi, additional, Okuyama, Hiromi, additional, Ourednik, Jitka, additional, Ourednik, Vaclav, additional, Oyamada, Masahito, additional, Oyamada, Yumiko, additional, Papaioannou, Virginia E., additional, Park, Kook I., additional, Patterson, Ethan S., additional, Patterson, Larry T., additional, Pébay, Alice, additional, Pera, Martin F., additional, Perea-Gomez, Aitana, additional, Perry, Anthony C.F., additional, Petitte, James N., additional, Phillips, Blaine W., additional, Potter, S. Steven, additional, Rai, Arti K., additional, Reeve, Christopher, additional, Reubinoff, Benjamin, additional, Rossant, Janet, additional, Rubart, Michael, additional, Savatier, Pierre, additional, Schöler, Hans, additional, Schulz, Cordula, additional, Schultz, Nikolaus, additional, Shamblott, Michael J., additional, Sidman, Richard L., additional, Simon, M. Celeste, additional, Snyder, Evan Y., additional, Stewart, A. Francis, additional, Studer, Lorenz, additional, Surani, Azim, additional, Takamatsu, Tetsuro, additional, Teng, Yang D., additional, Thesleff, Irma, additional, Thomson, James A., additional, Tosh, David, additional, Trainor, Paul, additional, Trounson, Alan O., additional, Tsuneto, Motokazu, additional, Tummers, Mark, additional, Upjohn, Edward, additional, Varigos, George, additional, Vernochet, Cécile, additional, Vivian, Jay L., additional, Wang, Zhongde, additional, Weir, Gordon C., additional, Wert, Susan E., additional, Whitsett, Jeffrey A., additional, Wininger, J. David, additional, Wu, Zhuoru, additional, Xu, Chunhui, additional, Yamane, Toshiyuki, additional, Yamashita, Jun, additional, Yamashita, Yukiko M., additional, Yamazaki, Hidetoshi, additional, Zoloth, Laurie, additional, Zwaka, Thomas P., additional, and Zweigerdt, Robert, additional

Published
2004
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10. Generation of germ cells from pluripotent stem cells in mammals

Author

Hayashi, Masafumi, Kawaguchi, Takamasa, Durcova-Hills, Gabriela, Imai, Hiroshi, Hayashi, Masafumi, Kawaguchi, Takamasa, Durcova-Hills, Gabriela, and Imai, Hiroshi

Abstract

[Background]The germ cell lineage transmits genetic and epigenetic information to the next generation. Primordial germ cells (PGCs), the early embryonic precursors of sperm or eggs, have been studied extensively. Recently, in vitro models of PGC induction have been established in the mouse. Many attempts are reported to enhance our understanding of PGC development in other mammals, including human. [Methods]Here, original and review articles that have been published on PubMed are reviewed in order to give an overview of the literature that is focused on PGC development, including the specification of in vivo and in vitro in mice, human, porcine, and bovine. [Results]Mammalian PGC development, in vivo and in vitro, have been studied primarily by using the mouse model as a template to study PGC specification in other mammals, including human, porcine, and bovine. [Conclusion]The growing body of published works reveals similarities, as well as differences, in PGC establishment in and between mouse and human.

Published
2018

21. Potential of fetal germ cells for nuclear transfer in cattle

Author

Zakhartchenko, Valeri, primary, Durcova-Hills, Gabriela, additional, Schernthaner, Wolfgang, additional, Stojkovic, Miodrag, additional, Reichenbach, Horst-Dieter, additional, Mueller, Sigrid, additional, Steinborn, Ralf, additional, Mueller, Mathias, additional, Wenigerkind, Hendrik, additional, Prelle, Katja, additional, Wolf, Eckhard, additional, and Brem, Gottfried, additional

Published
1999
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25. Developmental fate of embryonic germ cells (EGCs), in vivo andin vitro.

Author

Durcova-Hills, Gabriela, Wianny, Florence, Merriman, Julie, Zernicka-Goetz, Magdalena, and McLaren, Anne

Subjects
GERM cells, CELL lines, EMBRYOLOGY, CELL differentiation
Abstract

Abstract Embryonic germ cells (EGCs) derived from mouse primordial germ cells (PGCs) are known both to colonize all cell lineages of the fetus and to make tumors in vivo. When aggregated with eight-cell embryos, EGCs from a new EGC line expressing green fluorescent protein (GFP) were found to contribute preferentially to the epiblast but unexpectedly were also capable of colonizing primary endoderm. When injected under the kidney capsule, EGCs derived from 12.5 days post coitum (dpc) PGCs formed differentiated tumors. The ability of EGCs to differentiate in an organ culture system depends upon their partners in cell culture. When EGCs, marked with a LacZ transgene, were mixed with disaggregated and reaggregated mouse fetal lung in an organ culture system, they remained undifferentiated. In urogenital ridge reaggregates on the other hand, some EGCs were capable of differentiating to form small epithelial cysts. [ABSTRACT FROM AUTHOR]

Published
2003
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26. On the fate of primordial germ cells injected into early mouse embryos

Author

Leitch, Harry G., Okamura, Daiji, Durcova-Hills, Gabriela, Stewart, Colin L., Gardner, Richard L., Matsui, Yasuhisa, and Papaioannou, Virginia E.

Subjects
Pluripotency, endocrine system, Germline, urogenital system, embryonic structures, fungi, Primordial germ cells, Cell Biology, Molecular Biology, Developmental Biology
Abstract

Primordial germ cells (PGCs) are the founder cells of the germline. Via gametogenesis and fertilisation this lineage generates a new embryo in the next generation. PGCs are also the cell of origin of multilineage teratocarcinomas. In vitro, mouse PGCs can give rise to embryonic germ (EG) cells – pluripotent stem cells that can contribute to primary chimaeras when introduced into pre-implantation embryos. Thus, PGCs can give rise to pluripotent cells in the course of the developmental cycle, during teratocarcinogenesis and by in vitro culture. However, there is no evidence that PGCs can differentiate directly into somatic cell types. Furthermore, it is generally assumed that PGCs do not contribute to chimaeras following injection into the early mouse embryo. However, these data have never been formally published. Here, we present the primary data from the original PGC-injection experiments performed 40 years ago, alongside results from more recent studies in three separate laboratories. These results have informed and influenced current models of the relationship between pluripotency and the germline cycle. Current technologies allow further experiments to confirm and expand upon these findings and allow definitive conclusions as to the developmental potency of PGCs.

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28. Development of germ cells in the mouse.

Author

Durcova-Hills G and Capel B

Subjects
Animals, Cell Cycle, Cell Lineage, Cell Movement, Epigenesis, Genetic, Female, Gonads cytology, Gonads embryology, Gonads metabolism, Male, Mice, Pluripotent Stem Cells cytology, Pluripotent Stem Cells metabolism, Sex Characteristics, Sexual Development, Cell Differentiation, Germ Cells cytology, Germ Cells metabolism
Abstract

In mammals, germ cells are induced from a population of cells at the base of the allantois. This regulative mechanism of germ line induction depends on Bmp signals and a combination of epigenetic changes that silence somatic differentiation genes and activate pluripotency genes. RNA binding proteins are a conserved feature of germ cell development in mammals, and play critical roles in the establishment and maintenance of pluripotency. After their specification, germ cells move through the gut to the gonads under the influence of migratory and attractive cues. In the gonad, germ cells initiate sex-specific differentiation. Germ cells that arrive in the ovary enter meiosis, whereas germ cells that arrive in the testis undergo mitotic arrest. Entry into meiosis is controlled by retinoic acid signals that are blocked in the testis. The signals regulating mitotic arrest in the testis are still not completely understood, but likely involve RNA-binding proteins. Epigenetic reprograming occurs during specification, migratory stages, and sex-specific stages, when maternal and paternal imprints are established. The facility of transitions between germ cells and stem cells suggests a close relationship among their genomic programs.

Published
2008
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