Skip to main content
SpringerLink
Log in

Modern Technologies Deriving Human Primordial Germ Cells in vitro

  • Review
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Primordial germ cells (PGCs) are a unique type of stem cells capable of giving rise to totipotent stem cells and ensuring the fertility of an organism and the transfer of its genome to the next generation. PGC research is an important perspective research field of developmental biology that handles many questions of embryogenesis and holds promise for treatments of infertility in the future. Considering ethical concerns related to human embryos, the main research approach in understanding the biology of human PGCs is in vitro studies. In this review, we consider the historical perspective of human PGC studies in vitro, the main existing models, and further outlooks and applications in medicine and science.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BMP:

bone morphogenetic protein

EBs:

embryoid bodies

ESCs:

embryonic stem cells

hFGSCs:

human fetal gonadal stromal cells

hPGCs:

human primordial germ cells

(i)PSCs:

(induced) pluripotent stem cells

PGCs:

primordial germ cells

TNAP:

tissue-nonspecific alkaline phosphatase

References

  1. Kurimoto, K., Yabuta, Y., Ohinata, Y., Shigeta, M., Yamanaka, K., and Saitou, M. (2008) Complex genome–wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice, Genes Dev., 22, 1617–1635, doi: 10.1101/gad.1649908.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tanaka, S. S., Yamaguchi, Y. L., Tsoi, B., Lickert, H., and Tam, P. P. (2005) IFITM/mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primor–dial germ cell homing and repulsion, Dev. Cell, 9, 745–756, doi: 10.1016/j.devcel.2005.10.010.

    Article  CAS  PubMed  Google Scholar 

  3. Ginsburg, M., Snow, M. H., and McLaren, A. (1990) Primordial germ cells in the mouse embryo during gastrula–tion, Development, 110, 521–528.

    CAS  PubMed  Google Scholar 

  4. Irie, N., Tang, W. W., and Azim Surani, M. (2014) Germ cell specification and pluripotency in mammals: a perspective from early embryogenesis, Reprod. Med. Biol., 13, 203–215.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Saitou, M., and Yamaji, M. (2010) Germ cell specification in mice: signaling, transcription regulation, and epigenetic consequences, Reproduction, 139, 931–942.

    Article  CAS  PubMed  Google Scholar 

  6. De Felici, M. (2013) Origin, migration, and proliferation of human primordial germ cells, in Oogenesis (Coticchio, G., Albertini, D. F., and De Santis, L., eds.) Springer, London, pp. 19–38.

    Google Scholar 

  7. Leitch, H. G., Tang, W. W., and Surani, M. A. (2013) Primordial germ–cell development and epigenetic repro–gramming in mammals, Curr. Top. Dev. Biol., 104, 149–187.

    Article  CAS  PubMed  Google Scholar 

  8. Kozhukhar, V. G. (2011) Primordial germ cells in mammals and human. Origin, identification, migration, Tsitologiya, 53, 211–220.

    CAS  Google Scholar 

  9. Lawson, K. A., Dunn, N. R., Roelen, B. A., Zeinstra, L. M., Davis, A. M., Wright, C. V., Korving, J. P., and Hogan, B. L. (1999) Mouse embryo Bmp4 is required for the generation of primordial germ cells in the mouse embryo, Genes Dev., 13, 424–436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ohinata, Y., Ohta, H., Shigeta, M., Yamanaka, K., Wakayama, T., and Saitou, M. (2009) A signaling principle for the specification of the germ cell lineage in mice, Cell, 137, 571–584, doi: 10.1016/j.cell.2009.03.014.

    Article  CAS  PubMed  Google Scholar 

  11. Okamura, D., Hayashi, K., and Matsui, Y. (2005) Mouse epiblasts change responsiveness to BMP4 signal required for PGC formation through functions of extraembryonic ectoderm, Mol. Reprod. Dev., 70, 20–29.

    Article  CAS  PubMed  Google Scholar 

  12. Ying, Y., and Zhao, G. Q. (2001) Cooperation of ento–derm–derived BMP2 and extraembryonic ectoderm–derived BMP4 in primordial germ cell generation in the mouse, Dev. Biol., 232, 484–492.

    Article  CAS  PubMed  Google Scholar 

  13. Lange, U. C., Saitou, M., Western, P. S., Barton, S. C., and Surani, M. A. (2003) The fragilis interferon–inducible gene family of transmembrane proteins is associated with germ cell specification in mice, BMC Dev. Biol., 3, 1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ohinata, Y., Payer, B., O’Carroll, D., Ancelin, K., Ono, Y., Sano, M., Barton, S. C., Obukhanych, T., Nussenzweig, M., Tarakhovsky, A., and Surani, M. A. (2005) Blimp1 is a critical determinant of the germ cell lineage in mice, Nature, 436, 207–213.

    Article  CAS  PubMed  Google Scholar 

  15. Kehler, J., Tolkunova, E., Koschorz, B., Pesce, M., Gentile, L., Boiani, M., Lomeli, H., Nagy, A., McLaughlin, K. J., Scholer, H. R., and Tomilin, A. (2004) Oct4 is required for primordial germ cell survival, EMBO Rep., 5, 1078–1083.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Okamura, D., Tokitake, Y., Niwa, H., and Matsui, Y. (2008) Requirement of Oct3/4 function for germ cell spec–ification, Dev. Biol., 317, 576–584.

    Article  CAS  PubMed  Google Scholar 

  17. Chambers, I., Silva, J., Colby, D., Nichols, J., Nijmeijer, B., Robertson, M., Vrana, J., Jones, K., Grotewold, L., and Smith, A. (2007) Nanog safeguards pluripotency and medi–ates germline development, Nature, 450, 1230–1234.

    Article  CAS  PubMed  Google Scholar 

  18. Yamaguchi, S., Kurimoto, K., Yabuta, Y., Sasaki, H., Nakatsuji, N., Saitou, M., and Tada, T. (2009) Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells, Development, 136, 4011–4020.

    Article  CAS  PubMed  Google Scholar 

  19. Murakami, K., Gunesdogan, U., Zylicz, J. J., Tang, W. W. C., Sengupta, R., Kobayashi, T., Kim, S., Butler, R., Dietmann, S., and Surani, A. M. (2016) NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers, Nature, 529, 1–22.

    Article  CAS  Google Scholar 

  20. Yamaji, M., Seki, Y., Kurimoto, K., Yabuta, Y., Yuasa, M., Shigeta, M., Yamanaka, K., Ohinata, Y., and Saitou, M. (2008) Critical function of Prdm14 for the establishment of the germ cell lineage in mice, Nat. Genet., 40, 1016–1022.

    Article  CAS  PubMed  Google Scholar 

  21. Grabole, N., Tischler, J., Hackett, J. A., Kim, S., Tang, F., Leitch, H. G., Magnusdottir, E., and Surani, M. A. (2013) Prdm14 promotes germline fate and naive pluripotency by repressing FGF signalling and DNA methylation, EMBO Rep., 14, 629–637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Gell, J. J., Zhao, J., Chen, D., Hunt, T. J., and Clark, A. T. (2018) PRDM14 is expressed in germ cell tumors with con–stitutive overexpression altering human germline differenti–ation and proliferation, Stem Cell Res., 27, 46–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Weber, S., Eckert, D., Nettersheim, D., Gillis, A. J., Schafer, S., Kuckenberg, P., Ehlermann, J., Werling, U., Biermann, K., Looijenga, L. H., and Schorle, H. (2010) Critical function of AP–2 gamma/TCFAP2C in mouse embryonic germ cell maintenance, Biol. Reprod., 82, 214–223.

    Article  CAS  PubMed  Google Scholar 

  24. Kumar, D. L., and Defalco, T. (2017) Of mice and men: in vivo and in vitro studies of primordial germ cell specifica–tion, Semin. Reprod. Med., 35, 139–146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Vincent, S. D. (2005) The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis for–mation but is required for specification of primordial germ cells in the mouse, Development, 132, 1315–1325.

    Article  CAS  PubMed  Google Scholar 

  26. Irie, N., Weinberger, L., Tang, W. W., Kobayashi, T., Viukov, S., Manor, Y. S., Dietmann, S., Hanna, J. H., and Surani, M. A. (2015) SOX17 is a critical specifier of human primordial germ cell fate, Cell, 160, 253–268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tsuda, M., Sasaoka, Y., Kiso, M., Abe, K., Haraguchi, S., Kobayashi, S., and Saga, Y. (2003) Conserved role of nanos proteins in germ cell development, Science, 301, 1239–1241.

    Article  CAS  PubMed  Google Scholar 

  28. Suzuki, H., Tsuda, M., Kiso, M., and Saga, Y. (2008) Nanos3 maintains the germ cell lineage in the mouse by suppressing both Bax–dependent and–independent apop–totic pathways, Dev. Biol., 318, 133–142.

    Article  CAS  PubMed  Google Scholar 

  29. Tanaka, S. S., Toyooka, Y., Akasu, R., Katoh–Fukui, Y., Nakahara, Y., Suzuki, R., Yokoyama, M., and Noce, T. (2000) The mouse homolog of Drosophila Vasa is required for the development of male germ cells, Genes Dev., 14, 841–853.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Panula, S., Reda, A., Stukenborg, J.–B. B., Ramathal, C., Sukhwani, M., Albalushi, H., Edsgard, D., Nakamura, M., Soder, O., Orwig, K. E., Yamanaka, S., Reijo Pera, R. A., and Hovatta, O. (2016) Over expression of NANOS3 and DAZL in human embryonic stem cells, PLoS One, 11, e0165268.

    Book  Google Scholar 

  31. Schrans–Stassen, B. H., Saunders, P. T., Cooke, H. J., and de Rooij, D. G. (2001) Nature of the spermatogenic arrest in Dazl−/− mice, Biol. Reprod., 65, 771–776.

    Article  PubMed  Google Scholar 

  32. Buehr, M., McLaren, A., Bartley, A., and Darling, S. (1993) Proliferation and migration of primordial germ cells in We/We mouse embryos, Dev. Dyn., 198, 182–189.

    Article  CAS  PubMed  Google Scholar 

  33. Kudo, T., Kaneko, M., Iwasaki, H., Togayachi, A., Nishihara, S., Abe, K., and Narimatsu, H. (2004) Normal embryonic and germ cell development in mice lacking α1,3–fucosyltransferase IX (Fut9) which show disappear–ance of stage–specific embryonic antigen 1, Mol. Cell. Biol., 24, 4221–4228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Payer, B., Saitou, M., Barton, S. C., Thresher, R., Dixon, J. P. C., Zahn, D., Colledge, W. H., Carlton, M. B., Nakano, T., and Surani, M. A. (2003) Stella is a maternal effect gene required for normal early development in mice, Curr. Biol., 13, 2110–2117.

    Article  CAS  PubMed  Google Scholar 

  35. Saitou, M., Kagiwada, S., and Kurimoto, K. (2012) Epigenetic reprogramming in mouse pre–implantation development and primordial germ cells, Development, 139, 15–31.

    Article  CAS  PubMed  Google Scholar 

  36. De Felici, M. (2009) Primordial germ cell biology at the beginning of the XXI century, Int. J. Dev. Biol., 53, 891–894.

    Article  PubMed  Google Scholar 

  37. Liu, P., Wakamiya, M., Shea, M. J., Albrecht, U., Behringer, R. R., and Bradley, A. (1999) Requirement for Wnt3 in vertebrate axis formation, Nat. Genet., 22, 361–365.

    Article  CAS  PubMed  Google Scholar 

  38. Yoon, Y., Huang, T., Tortelote, G. G., Wakamiya, M., Hadjantonakis, A. K., Behringer, R. R., and Rivera–Perez, J. A. (2015) Extra–embryonic Wnt3 regulates the establish–ment of the primitive streak in mice, Dev. Biol., 403, 80–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. McKay, D. G., Hertig, A. T., Adams, E. C., and Danziger, S. (1953) Histochemical observations on the germ cells of human embryos, Anat. Rec., 117, 201–219.

    Article  CAS  PubMed  Google Scholar 

  40. Kellokumpu–Lehtinen, P. L., and Soderstrom, K. O. (1978) Occurrence of nuage in fetal human germ cells, Cell Tissue Res., 194, 171–177.

    Article  PubMed  Google Scholar 

  41. Findley, S. D., Tamanaha, M., Clegg, N. J., and Ruohola–Baker, H. (2003) Maelstrom, a Drosophila spindle–class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage, Development, 130, 859–871.

    CAS  PubMed  Google Scholar 

  42. Ishidate, T., Ozturk, A. R., Durning, D. J., Sharma, R., Shen, E. Z., Chen, H., Seth, M., Shirayama, M., and Mello, C. C. (2018) ZNFX–1 functions within perinuclear nuage to balance epigenetic signals, Mol. Cell, 70, 639–649.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Soper, S. F. C., van der Heijden, G. W., Hardiman, T. C., Goodheart, M., Martin, S. L., de Boer, P., and Bortvin, A. (2008) Mouse maelstrom, a component of nuage, is essen–tial for spermatogenesis and transposon repression in meio–sis, Dev. Cell, 15, 285–297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Morohaku, K., Tanimoto, R., Sasaki, K., Kawahara–Miki, R., Kono, T., Hayashi, K., Hirao, Y., and Obata, Y. (2016) Complete in vitro generation of fertile oocytes from mouse primordial germ cells, Proc. Natl. Acad. Sci. USA, 113, 9021–9026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhou, Q., Wang, M., Yuan, Y., Wang, X., Fu, R., Wan, H., Hirao, Y., and Zhou, Q. (2016) Complete meiosis from embryonic stem cell–derived germ cells in vitro, Cell Stem Cell, 18, 330–340.

    Article  CAS  PubMed  Google Scholar 

  46. Turnpenny, L., Brickwood, S., Spalluto, C. M., Piper, K., Cameron, I. T., Wilson, D. I., and Hanley, N. A. (2003) Derivation of human embryonic germ cells: an alternative source of pluripotent stem cells, Stem Cells, 21, 598–609.

    Article  PubMed  Google Scholar 

  47. Clark, A. T., Bodnar, M. S., Fox, M., Rodriquez, R. T., Abeyta, M. J., Firpo, M. T., and Pera, R. A. (2004) Spontaneous differentiation of germ cells from human embryonic stem cells in vitro, Hum. Mol. Genet., 13, 727–739.

    Article  CAS  PubMed  Google Scholar 

  48. Tilgner, K., Atkinson, S. P., Golebiewska, A., Stojkovic, M., Lako, M., and Armstrong, L. (2008) Isolation of pri–mordial germ cells from differentiating human embryonic stem cells, Stem Cells, 26, 3075–3085.

    Article  CAS  PubMed  Google Scholar 

  49. Kee, K., Gonsalves, J. M., Clark, A. T., and Pera, R. A. (2006) Bone morphogenetic proteins induce germ cell dif–ferentiation from human embryonic stem cells, Stem Cells Dev., 15, 831–837.

    Article  CAS  PubMed  Google Scholar 

  50. Hubner, K., Fuhrmann, G., Christenson, L. K., Kehler, J., Reinbold, R., De La Fuente, R., Wood, J., Strauss, J. F., 3rd, Boiani, M., and Scholer, H. R. (2003) Derivation of oocytes from mouse embryonic stem cells, Science, 300, 1251–1256.

    Article  CAS  PubMed  Google Scholar 

  51. Geijsen, N., Horoschak, M., Kim, K., Gribnau, J., Eggan, K., Daley, G. Q., Change, G., and Jaarsveld, V. (2004) Derivation of embryonic germ cells and male gametes from embryonic stem cells, Nature, 427, 148–154.

    Article  CAS  PubMed  Google Scholar 

  52. Park, T. S., Galic, Z., Conway, A. E., Lindgren, A., Van Handel, B. J., Magnusson, M., Richter, L., Teitell, M. A., Mikkola, H. K., Lowry, W. E., Plath, K., and Clark, A. T. (2009) Derivation of primordial germ cells from human embryonic and induced pluripotent stem cells is signifi–cantly improved by coculture with human fetal gonadal cells, Stem Cells, 27, 783–795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Panula, S., Medrano, J. V., Kee, K., Bergstrom, R., Nguyen, H. N., Byers, B., Wilson, K. D., Wu, J. C., Simon, C., Hovatta, O., and Reijo Pera, R. A. (2011) Human germ cell differentiation from fetal–and adult–derived induced pluripotent stem cells, Hum. Mol. Genet., 20, 752–762.

    Article  CAS  PubMed  Google Scholar 

  54. Eguizabal, C., Montserrat, N., Vassena, R., Barragan, M., Garreta, E., Garcia–Quevedo, L., Vidal, F., Giorgetti, A., Veiga, A., and Izpisua Belmonte, J. C. (2011) Complete meiosis from human induced pluripotent stem cells, Stem Cells, 29, 1186–1195.

    Article  CAS  PubMed  Google Scholar 

  55. Xie, L., Lin, L., Tang, Q., Li, W., Huang, T., Huo, X., Liu, X., Jiang, J., He, G., and Ma, L. (2015) Sertoli cell–medi–ated differentiation of male germ cell–like cells from human umbilical cord Wharton’s jelly–derived mesenchymal stem cells in an in vitro co–culture system, Eur. J. Med. Res., 20, 9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Fujimoto, T., Miyayama, Y., and Fuyuta, M. (1977) The origin, migration and fine morphology of human primor–dial germ cells, Anat. Rec., 188, 315–329.

    Article  CAS  PubMed  Google Scholar 

  57. Funkuda, T. (1976) Ultrastructure of primordial germ cells in human embryo, Virchows Arch. B Cell Pathol., 20, 85–89.

    CAS  PubMed  Google Scholar 

  58. Castrillon, D. H., Quade, B. J., Wang, T. Y., Quigley, C., and Crum, C. P. (2000) The human VASA gene is specifi–cally expressed in the germ cell lineage, Proc. Natl. Acad. Sci. USA, 97, 9585–9590.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Eguizabal, C., Herrera, L., De Onate, L., Montserrat, N., Hajkova, P., and Izpisua Belmonte, J. C. (2016) Characterization of the epigenetic changes during human gonadal primordial germ cells reprogramming, Stem Cells, 34, 2418–2428.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Kerr, C. L., Hill, C. M., Blumenthal, P. D., and Gearhart, J. D. (2008) Expression of pluripotent stem cell markers in the human fetal ovary, Hum. Reprod., 23, 589–599.

    Article  CAS  PubMed  Google Scholar 

  61. Kerr, C. L., Hill, C. M., Blumenthal, P. D., and Gearhart, J. D. (2008) Expression of pluripotent stem cell markers in the human fetal testis, Stem Cells, 26, 412–421.

    Article  PubMed  Google Scholar 

  62. Leng, L., Tan, Y., Gong, F., Hu, L., Ouyang, Q., Zhao, Y., Lu, G., and Lin, G. (2015) Differentiation of primordial germ cells from induced pluripotent stem cells of primary ovarian insufficiency, Hum. Reprod., 30, 737–748.

    Article  CAS  PubMed  Google Scholar 

  63. Medrano, J. V., Ramathal, C., Nguyen, H. N., Simon, C., and Reijo Pera, R. A. (2012) Divergent RNA–binding pro–teins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro, Stem Cells, 30, 441–451.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhao, Y., Ye, S., Liang, D., Wang, P., Fu, J., Ma, Q., Kong, R., Shi, L., Gong, X., Chen, W., Ding, W., Yang, W., Zhu, Z., Chen, H., Sun, X., Zhu, J., Li, Z., and Wang, Y. (2018) In vitro modeling of human germ cell development using pluripotent stem cells, Stem Cell Rep., 10, 509–523.

    Article  Google Scholar 

  65. Lin, I. Y., Chiu, F. L., Yeang, C. H., Chen, H. F., Chuang, C. Y., Yang, S. Y., Hou, P. S., Sintupisut, N., Ho, H. N., Kuo, H. C., and Lin, K. I. (2014) Suppression of the SOX2 neural effector gene by PRDM1 promotes human germ cell fate in embryonic stem cells, Stem Cell Rep., 2, 189–204.

    Article  CAS  Google Scholar 

  66. Hayashi, Y., Saitou, M., and Yamanaka, S. (2012) Germline development from human pluripotent stem cells toward disease modeling of infertility, Fertil. Steril., 97, 1250–1259.

    Article  PubMed  Google Scholar 

  67. Angeles Julaton, V. T., and Reijo Pera, R. A. (2011) NANOS3 function in human germ cell development, Hum. Mol. Genet., 20, 2238–2250.

    Article  CAS  Google Scholar 

  68. Gkountela, S., Li, Z., Vincent, J. J., Zhang, K. X., Chen, A., Pellegrini, M., and Clark, A. T. (2013) The ontogeny of cKIT+ human primordial germ cells proves to be a resource for human germ line reprogramming, imprint erasure and in vitro differentiation, Nat. Cell Biol., 15, 113–122.

    Article  CAS  PubMed  Google Scholar 

  69. Hackett, J. A., Zylicz, J. J., and Surani, M. A. (2012) Parallel mechanisms of epigenetic reprogramming in the germline, Trends Genet., 28, 164–174.

    Article  CAS  PubMed  Google Scholar 

  70. Hara, K., Kanai–Azuma, M., Uemura, M., Shitara, H., Taya, C., Yonekawa, H., Kawakami, H., Tsunekawa, N., Kurohmaru, M., and Kanai, Y. (2009) Evidence for crucial role of hindgut expansion in directing proper migration of primordial germ cells in mouse early embryogenesis, Dev. Biol., 330, 427–439.

    Article  CAS  PubMed  Google Scholar 

  71. Perrett, R. M., Turnpenny, L., Eckert, J. J., O’Shea, M., Sonne, S. B., Cameron, I. T., Wilson, D. I., Rajpert–De Meyts, E., and Hanley, N. A. (2008) The early human germ cell lineage does not express SOX2 during in vivo develop–ment or upon in vitro culture, Biol. Reprod., 78, 852–858.

    Article  CAS  PubMed  Google Scholar 

  72. West, J. A., Viswanathan, S. R., Yabuuchi, A., Cunniff, K., Takeuchi, A., Park, I. H., Sero, J. E., Zhu, H., Perez–Atayde, A., Frazier, A. L., Surani, M. A., and Daley, G. Q. (2009) A role for Lin28 in primordial germ–cell develop–ment and germ–cell malignancy, Nature, 460, 909–913.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Easley, C. A., Phillips, B. T., McGuire, M. M., Barringer, J. M., Valli, H., Hermann, B. P., Simerly, C. R., Rajkovic, A., Miki, T., Orwig, K. E., and Schatten, G. P. (2012) Direct differentiation of human pluripotent stem cells into haploid spermatogenic cells, Cell Rep., 2, 440–446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Gafni, O., Weinberger, L., Mansour, A. A., Manor, Y. S., Chomsky, E., Ben–Yosef, D., Kalma, Y., Viukov, S., Maza, I., Zviran, A., Rais, Y., Shipony, Z., Mukamel, Z., Krupalnik, V., Zerbib, M., Geula, S., Caspi, I., Schneir, D., Shwartz, T., Gilad, S., Amann–Zalcenstein, D., Benjamin, S., Amit, I., Tanay, A., Massarwa, R., Novershtern, N., and Hanna, J. H. (2013) Derivation of novel human ground state naive pluripotent stem cells, Nature, 504, 282–286.

    Article  CAS  PubMed  Google Scholar 

  75. Kilens, S., Meistermann, D., Moreno, D., Chariau, C., Gaignerie, A., Reignier, A., Lelievre, Y., Casanova, M., Vallot, C., Nedellec, S., Flippe, L., Firmin, J., Song, J., Charpentier, E., Lammers, J., Donnart, A., Marec, N., Deb, W., Bihouee, A., Le Caignec, C., Pecqueur, C., Redon, R., Barriere, P., Bourdon, J., Pasque, V., Soumillon, M., Mikkelsen, T. S., Rougeulle, C., Freour, T., David, L., Abel, L., Alcover, A., Astrom, K., Bousso, P., Bruhns, P., Cumano, A., Duffy, D., Demangel, C., Deriano, L., DI Santo, J., Dromer, F., Eberl, G., Enninga, J., Fellay, J., Freitas, A., Gelpi, O., Gomperts–Boneca, I., Hercberg, S., Lantz, O., Leclerc, C., Mouquet, H., Patin, E., Pellegrini, S., Pol, S., Rogge, L., Sakuntabhai, A., Schwartz, O., Schwikowski, B., Shorte, S., Soumelis, V., Tangy, F., Tartour, E., Toubert, A., Ungeheuer, M. N., Quintana–Murci, L., and Albert, M. L. (2018) Parallel der–ivation of isogenic human primed and naive induced pluripotent stem cells, Nat. Commun., 9, 1–13.

    Article  CAS  Google Scholar 

  76. Theunissen, T. W., Friedli, M., He, Y., Planet, E., O’Neil, R. C., Markoulaki, S., Pontis, J., Wang, H., Iouranova, A., Imbeault, M., Duc, J., Cohen, M. A., Wert, K. J., Castanon, R., Zhang, Z., Huang, Y., Nery, J. R., Drotar, J., Lungjangwa, T., Trono, D., Ecker, J. R., and Jaenisch, R. (2016) Molecular criteria for defining the naive human pluripotent state, Cell Stem Cell, 19, 502–515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Ware, C. B., Nelson, A. M., Mecham, B., Hesson, J., Zhou, W., Jonlin, E. C., Jimenez–Caliani, A. J., Deng, X., Cavanaugh, C., Cook, S., Tesar, P. J., Okada, J., Margaretha, L., Sperber, H., Choi, M., Blau, C. A., Treuting, P. M., Hawkins, R. D., Cirulli, V., and Ruohola–Baker, H. (2014) Derivation of naive human embryonic stem cells, Proc. Natl. Acad. Sci. USA, 111, 4484–4489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Watanabe, K., Ueno, M., Kamiya, D., Nishiyama, A., Matsumura, M., Wataya, T., Takahashi, J. B., Nishikawa, S., Nishikawa, S. I., Muguruma, K., and Sasai, Y. (2007) A ROCK inhibitor permits survival of dissociated human embryonic stem cells, Nat. Biotechnol., 25, 681–686.

    Article  CAS  PubMed  Google Scholar 

  79. Chuang, C. Y., Lin, K. I., Hsiao, M., Stone, L., Chen, H. F., Huang, Y. H., Lin, S. P., Ho, N. N., and Kuo, H. C. (2012) Meiotic competent human germ cell–like cells derived from human embryonic stem cells induced by BMP4/WNT3A signaling and OCT4/EpCAM (epithelial cell adhesion molecule) selection, J. Biol. Chem., 287, 14389–14401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Sugawa, F., Arauzo–Bravo, M. J., Yoon, J., Kim, K.–P., Aramaki, S., Wu, G., Stehling, M., Psathaki, O. E., Hubner, K., and Scholer, H. R. (2015) Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile, EMBO J., 34, 1009–1024.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bernardo, A. S., Faial, T., Gardner, L., Niakan, K. K., Ortmann, D., Senner, C. E., Callery, E. M., Trotter, M. W., Hemberger, M., Smith, J. C., Bardwell, L., Moffett, A., and Pedersen, R. A. (2011) BRACHYURY and CDX2 mediate BMP–induced differentiation of human and mouse pluripotent stem cells into embryonic and extraem–bryonic lineages, Cell Stem Cell, 9, 144–155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Aramaki, S., Hayashi, K., Kurimoto, K., Ohta, H., Yabuta, Y., Iwanari, H., Mochizuki, Y., Hamakubo, T., Kato, Y., Shirahige, K., and Saitou, M. (2013) A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants, Dev. Cell, 27, 516–529.

    Article  CAS  PubMed  Google Scholar 

  83. Sasaki, K., Yokobayashi, S., Nakamura, T., Okamoto, I., Yabuta, Y., Kurimoto, K., Ohta, H., Moritoki, Y., Iwatani, C., Tsuchiya, H., Nakamura, S., Sekiguchi, K., Sakuma, T., Yamamoto, T., Mori, T., Woltjen, K., Nakagawa, M., Yamamoto, T., Takahashi, K., Yamanaka, S., and Saitou, M. (2015) Robust in vitro induction of human germ cell fate from pluripotent stem cells, Cell Stem Cell, 17, 178–194.

    Article  CAS  PubMed  Google Scholar 

  84. Saitou, M., Barton, S. C., and Surani, M. A. (2002) A molecular programme for the specification of germ cell fate in mice, Nature, 418, 293–300.

    Article  CAS  PubMed  Google Scholar 

  85. Yamaji, M., Ueda, J., Hayashi, K., Ohta, H., Yabuta, Y., Kurimoto, K., Nakato, R., Yamada, Y., Shirahige, K., and Saitou, M. (2013) PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells, Cell Stem Cell, 12, 368–382.

    Article  CAS  PubMed  Google Scholar 

  86. Chen, D., Gell, J. J., Tao, Y., Sosa, E., and Clark, A. T. (2017) Modeling human infertility with pluripotent stem cells, Stem Cell Res., 21, 187–192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Singh, K., and Jaiswal, D. (2011) Human male infertility: a complex multifactorial phenotype, Reprod. Sci., 18, 418–425.

    Article  PubMed  Google Scholar 

  88. Bowles, J. (2006) Retinoid signaling determines germ cell fate in mice, Science, 312, 596–600.

    Article  CAS  PubMed  Google Scholar 

  89. MacLean, G., Li, H., Metzger, D., Chambon, P., and Petkovich, M. (2007) Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice, Endocrinology, 148, 4560–4567.

    Article  CAS  PubMed  Google Scholar 

  90. Abrao, M. S., Muzii, L., and Marana, R. (2013) Anatomical causes of female infertility and their manage–ment, Int. J. Gynecol. Obstet., 123, Suppl. 2, S18–S24.

    Google Scholar 

  91. Anawalt, B. D. (2013) Approach to male infertility and induction of spermatogenesis, J. Clin. Endocrinol. Metab., 98, 3532–3542.

    Article  CAS  Google Scholar 

  92. Rieger, D. (2012) Culture systems: physiological and envi–ronmental factors that can affect the outcome of human ART, Methods Mol. Biol., 912, 333–354.

    CAS  PubMed  Google Scholar 

  93. Sharpe, R. M. (2010) Environmental/lifestyle effects on spermatogenesis, Philos. Trans. R Soc. Lond B Biol. Sci., 365, 1697–1712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Handel, M. A., Eppig, J. J., and Schimenti, J. C. (2014) Applying “gold standards” to in vitro–derived germ cells, Cell, 157, 1257–1261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bourillot, P. Y., Aksoy, I., Schreiber, V., Wianny, F., Schulz, H., Hummel, O., Hubner, N., and Savatier, P. (2009) Novel STAT3 target genes exert distinct roles in the inhibition of mesoderm and entoderm differentiation in cooperation with Nanog, Stem Cells, 27, 1760–1771.

    Article  CAS  PubMed  Google Scholar 

  96. Daheron, L., Opitz, S. L., Zaehres, H., Lensch, W. M., Andrews, P. W., Itskovitz–Eldor, J., and Daley, G. Q. (2004) LIF/STAT3 signaling fails to maintain self–renewal of human embryonic stem cells, Stem Cells, 22, 770–778.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Lomonosov Moscow State University, Faculty of Biology, 119991, Moscow, Russia

    V. K. Abdyyev, I. V. Neklyudova, E. A. Vorotelyak & A. V. Vasiliev

  2. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    E. B. Dashinimayev, E. A. Vorotelyak & A. V. Vasiliev

  3. Pirogov Russian Research Medical University, 117997, Moscow, Russia

    E. B. Dashinimayev & E. A. Vorotelyak

Authors
  1. V. K. Abdyyev
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E. B. Dashinimayev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. V. Neklyudova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. A. Vorotelyak
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. V. Vasiliev
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. K. Abdyyev.

Additional information

Russian Text © V. K. Abdyyev, E. B. Dashinimayev, I. V. Neklyudova, E. A. Vorotelyak, A. V. Vasiliev, 2019, published in Biokhimiya, 2019, Vol. 84, No. 3, pp. 330–342.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Abdyyev, V.K., Dashinimayev, E.B., Neklyudova, I.V. et al. Modern Technologies Deriving Human Primordial Germ Cells in vitro. Biochemistry Moscow 84, 220–231 (2019). https://doi.org/10.1134/S0006297919030040

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297919030040

Keywords

Search

Navigation