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In vitro germline potential of stem cells derived from fetal porcine skin

Nature Cell Biology volume 8, pages 384–390 (2006)Cite this article

Abstract

Two of the unanswered questions in mammalian developmental biology are when and where the fate of the germ cell is specified. Here, we report that stem cells isolated from the skin of porcine fetuses have the intrinsic ability to differentiate into oocyte-like cells. When differentiation was induced, a subpopulation of these cells expressed markers such as Oct4, Growth differentiation factor 9b (GDF9b), the Deleted in Azoospermia-like (DAZL) gene and Vasa — all consistent with germ-cell formation. On further differentiation, these cells formed follicle-like aggregates that secreted oestradiol and progesterone and responded to gonadotropin stimulation. Some of these aggregates extruded large oocyte-like cells that expressed oocyte markers, such as zona pellucida, and the meiosis marker, synaptonemal complex protein 3 (SCP3). Some of these oocyte-like cells spontaneously developed into parthenogenetic embryo-like structures. The ability to generate oocyte-like cells from skin-derived cells may offer new possibilities for tissue therapy and provide a new in vitro model to study germ-cell formation and oogenesis.

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Figure 1: Germ-cell marker expression and generation of oocyte-cumulus-like complexes during differentiation.
Figure 2: Expression of oocyte markers and formation of meiosis-like morphology by oocyte-like cells.
Figure 3: Steroid production and regulation by gonadotropin during induced differentiation of skin-derived cells.
Figure 4: Development of structures resembling preimplantation embryos from oocyte-like cells.

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References

  1. Dyce, P. W., Zhu, H., Craig, J. & Li, J. Stem cells with multilineage potential derived from porcine skin. Biochem. Biophys. Res. Commun. 316, 651–658 (2004).

    Article  CAS  Google Scholar 

  2. Dube, J. L. et al. The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol. Endocrinol. 12, 1809–1817 (1998).

    Article  CAS  Google Scholar 

  3. Yen, P. H. Putative biological functions of the DAZ family. Int. J. Androl. 27, 125–129 (2004).

    Article  CAS  Google Scholar 

  4. Toyooka, Y. et al. Expression and intracellular localization of mouse Vasa-homologue protein during germ cell development. Mech. Dev. 93, 139–149 (2000).

    Article  CAS  Google Scholar 

  5. Paules, R. S., Buccione, R., Moschel, R. C., Vande Woude, G. F. & Eppig, J. J. Mouse Mos protooncogene product is present and functions during oogenesis. Proc. Natl Acad. Sci. USA 86, 5395–5399 (1989).

    Article  CAS  Google Scholar 

  6. Sagata, N., Oskarsson, M., Copeland, T., Brumbaugh, J. & Vande Woude, G. F. Function of c-mos proto-oncogene product in meiotic maturation in Xenopus oocytes. Nature 335, 519–525 (1988).

    Article  CAS  Google Scholar 

  7. Dunbar, B. S. et al. The mammalian zona pellucida: its biochemistry, immunochemistry, molecular biology, and developmental expression. Reprod. Fertil. Dev. 6, 331–347 (1994).

    Article  CAS  Google Scholar 

  8. Roeder, G. S. Meiotic chromosomes: it takes two to tango. Genes Dev. 11, 2600–2621 (1997).

    Article  CAS  Google Scholar 

  9. Parra, M. T. et al. Involvement of the cohesin Rad21 and SCP3 in monopolar attachment of sister kinetochores during mouse meiosis I. J. Cell Sci. 117, 1221–1234 (2004).

    Article  CAS  Google Scholar 

  10. Hillier, S. G., Whitelaw, P. F. & Smyth, C. D. Follicular oestrogen synthesis: the 'two-cell, two-gonadotrophin' model revisited. Mol. Cell Endocrinol. 100, 51–54 (1994).

    Article  CAS  Google Scholar 

  11. Richards, J. S. & Hedin, L. Molecular aspects of hormone action in ovarian follicular development, ovulation, and luteinization. Annu. Rev. Physiol. 50, 441–463 (1988).

    Article  CAS  Google Scholar 

  12. Kirchhof, N. et al. Expression pattern of Oct-4 in preimplantation embryos of different species. Biol. Reprod. 63, 1698–1705 (2000).

    Article  CAS  Google Scholar 

  13. Tam, P. P. & Zhou, S. X. The allocation of epiblast cells to ectodermal and germ-line lineages is influenced by the position of the cells in the gastrulating mouse embryo. Dev. Biol. 178, 124–132 (1996).

    Article  CAS  Google Scholar 

  14. Mintz, B. & Russell, E. S. Gene-induced embryological modifications of primordial germ cells in the mouse. J. Exp. Zool. 134, 207–237 (1957).

    Article  CAS  Google Scholar 

  15. Toma, J. G. et al. Isolation of multipotent adult stem cells from the dermis of mammalian skin. Nature Cell Biol. 3, 778–784 (2001).

    Article  CAS  Google Scholar 

  16. Johnson, J., Canning, J., Kaneko, T., Pru, J. K. & Tilly, J. L. Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428, 145–150 (2004).

    Article  CAS  Google Scholar 

  17. Taya, T., Yamasaki, N., Tsubamoto, H., Hasegawa, A. & Koyama, K. Cloning of a cDNA coding for porcine zona pellucida glycoprotein ZP1 and its genomic organization. Biochem. Biophys. Res. Commun. 207, 790–799 (1995).

    Article  CAS  Google Scholar 

  18. Spargo, S. C. & Hope, R. M. Evolution and nomenclature of the zona pellucida gene family. Biol. Reprod. 68, 358–362 (2003).

    Article  CAS  Google Scholar 

  19. Miyano, T. JSAR Outstanding Research Award. In vitro growth of mammalian oocytes. J. Reprod. Dev. 51, 169–176 (2005).

    Article  Google Scholar 

  20. O'Brien, M. J., Pendola, J. K. & Eppig, J. J. A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence. Biol. Reprod. 68, 1682–1686 (2003).

    Article  CAS  Google Scholar 

  21. Hubner, K. et al. Derivation of oocytes from mouse embryonic stem cells. Science 300, 1251–1256 (2003).

    Article  Google Scholar 

  22. Scholer, H. R., Hatzopoulos, A. K., Balling, R., Suzuki, N. & Gruss, P. A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J. 8, 2543–2550 (1989).

    Article  CAS  Google Scholar 

  23. Webb, R. et al. Mechanisms regulating follicular development and selection of the dominant follicle. Reprod. Suppl. 61, 71–90 (2003).

    CAS  Google Scholar 

  24. Jiang, J. Y., Cheung, C. K., Wang, Y. & Tsang, B. K. Regulation of cell death and cell survival gene expression during ovarian follicular development and atresia. Front. Biosci. 8, d222–d237 (2003).

    Article  CAS  Google Scholar 

  25. Godin, I. et al. Effects of the steel gene product on mouse primordial germ cells in culture. Nature 352, 807–809 (1991).

    Article  CAS  Google Scholar 

  26. Pesce, M., Di Carlo, A. & De Felici, M. The c-kit receptor is involved in the adhesion of mouse primordial germ cells to somatic cells in culture. Mech. Dev. 68, 37–44 (1997).

    Article  CAS  Google Scholar 

  27. Moe-Behrens, G. H. et al. Akt–PTEN signaling mediates estrogen-dependent proliferation of primordial germ cells in vitro. Mol. Endocrinol. 17, 2630–2638 (2003).

    Article  CAS  Google Scholar 

  28. Toyooka, Y., Tsunekawa, N., Akasu, R. & Noce, T. Embryonic stem cells can form germ cells in vitro. Proc. Natl Acad. Sci. USA 100, 11457–11462 (2003).

    Article  CAS  Google Scholar 

  29. Geijsen, N. et al. Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature 427, 148–154 (2004).

    Article  CAS  Google Scholar 

  30. Shim, H. & Anderson, G. B. In vitro survival and proliferation of porcine primordial germ cells. Theriogenology 49, 521–528 (1998).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank R. S. Prather for helpful discussion on the project, B. K. Tsang for critical reading and suggestions on the manuscript, N. Tanphaichitr for the anti-ZPC antibody, and the staff at the Arkell research station and the Meat Wing at the University of Guelph for their assistance in collecting porcine fetus samples. This worked was supported by the Premier's Research Excellence Award (J.L.), Natural Sciences and Engineering Research Council of Canada, Canada Foundation for Innovation and Ontario Pork. P. W. D. was a recipient of the Natural Sciences and Engineering Research Council of Canada (PGS-D) scholarship.

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  1. Department of Animal and Poultry Science, University of Guelph, Guelph, N1G 2W1, Ontario, Canada

    Paul W. Dyce, Lihua Wen & Julang Li

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  1. Paul W. Dyce
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Correspondence to Julang Li.

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Dyce, P., Wen, L. & Li, J. In vitro germline potential of stem cells derived from fetal porcine skin. Nat Cell Biol 8, 384–390 (2006). https://doi.org/10.1038/ncb1388

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