БИОХИМИЯ, 2019, том 84, вып. 3, с. 330–342
УДК 576.53
Современные технологии получения первичных половых клеток человека in vitro
Обзор
1 Московский государственный университет им. М.В. Ломоносова, биологический факультет, 119234 Россия, Москва; электронная почта: mailtovepa@gmail.com
2 Институт биологии развития им. Н.К. Кольцова РАН, 119334 Москва, Россия
3 Российский национальный исследовательский медицинский университет им. Н.И. Пирогова, 117997 Москва, Россия
Поступила в редакцию 14.09.2018
После доработки 20.11.2018
Принята к публикации 20.11.2018
DOI: 10.1134/S0320972519030047
КЛЮЧЕВЫЕ СЛОВА: первичные половые клетки, ППК, ИПСК, ЭСК, VASA, PRDM1, человек.
Аннотация
Первичные половые клетки (ППК) — уникальный тип стволовых клеток человека, способный дать начало тотипотентным стволовым клеткам и обеспечивающий фертильность организма и перенос генетической информации следующим поколениям. Исследования ППК являются важной областью биологии развития, в рамках которой проводится изучение фундаментальных проблем раннего эмбриогенеза, таких как механизмы обособления, эпигенетические перестройки и геномный импринтинг при дифференцировке ППК человека in vitro. На основе технологий получения ППК in vitro в перспективе возможна разработка новых способов лечения бесплодия и определение причин идиопатического бесплодия. С учетом этической специфики работы с эмбрионами человека основным методом исследования ППК человека является работа с клетками in vitro. В обзоре рассмотрены история вопроса исследований ППК человека in vitro, основные существующие модели и направления развития этой области.
Текст статьи
Сноски
* Адресат для корреспонденции.
Финансирование
Работа выполнена в рамках Государственного задания Института биологии развития им. Н.К. Кольцова РАН.
Конфликт интересов
Авторы заявляют об отсутствии конфликта интересов.
Список литературы
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.
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 primordial germ cell homing and repulsion, Dev. Cell., 9, 745–756, doi: 10.1016/j.devcel.2005.10.010.
3. Ginsburg, M., Snow, M.H., and McLaren, A. (1990) Primordial germ cells in the mouse embryo during gastrulation, Development, 110, 521–528.
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. doi: 10.1007/s12522-014-0184-2.
5. Saitou, M., and Yamaji, M. (2010) Germ cell specification in mice: signaling, transcription regulation, and epigenetic consequences, Reproduction, 139, 931–942, doi: 10.1530/REP-10-0043.
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, doi: 10.1007/978-0-85729-826-2.
7. Leitch, H.G., Tang, W.W., and Surani, M.A. (2013) Primordial germ-cell development and epigenetic reprogramming in mammals, Curr. Top. Dev. Biol., 104, 149–187, doi: 10.1016/B978-0-12-416027-9.00005-X.
8. Кожухарь В.Г. (2011) Первичные половые клетки млекопитающих и человека. Происхождение, идентификация, миграция, Цитология, 53, 211–220.
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.
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.
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, doi: 10.1002/mrd.20136.
12. Ying, Y., and Zhao, G.Q. (2001) Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse, Dev. Biol., 232, 484–492, doi: 10.1006/dbio.2001.0173.
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, doi: 10.1186/1471-213X-3-1.
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, doi: 10.1038/nature03813.
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, doi: 10.1038/sj.embor.7400279.
16. Okamura, D., Tokitake, Y., Niwa, H., and Matsui, Y. (2008) Requirement of Oct3/4 function for germ cell specification, Dev. Biol., 317, 576–584, doi: 10.1016/j.ydbio.2008.03.002.
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 mediates germline development, Nature, 450, 1230–1234, doi: 10.1038/nature06403.
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, doi: 10.1242/dev.041160.
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, doi: 10.1038/nature16480.
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, doi: 10.1038/ng.186.
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 Reports, 14, 629–637, doi:10.1038/embor.2013.67.
22. Gell, J.J., Zhao, J., Chen, D., Hunt, T.J., and Clark, A.T. (2018) PRDM14 is expressed in germ cell tumors with constitutive overexpression altering human germline differentiation and proliferation, Stem Cell Res., 27, 46–56, doi: 10.1016/j.scr.2017.12.016.
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, doi: 10.1095/biolreprod.109.078717.
24. Kumar, D.L., and Defalco, T. (2017) Of mice and men: in vivo and in vitro studies of primordial germ cell specification, Semin. Reprod. Med., 35, 139–146, doi: 10.1055/s-0037-1599085.
25. Vincent, S.D. (2005) The zinc finger transcriptional repressor Blimp1/Prdm1 is dispensable for early axis formation but is required for specification of primordial germ cells in the mouse, Development, 132, 1315–1325, doi: 10.1242/dev.01711.
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, doi: 10.1016/j.cell.2014.12.013.
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, doi: 10.1126/science.1085222.
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 apoptotic pathways, Dev. Biol., 318, 133–142, doi: 10.1016/j.ydbio.2008.03.020.
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, doi: 10.1101/gad.14.7.841.
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, doi: 10.1371/journal.pone.0165268.
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, doi: 10.1095/biolreprod65.3.771.
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, doi: 10.1002/aja.1001980304.
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 α disappearance of stage-specific embryonic antigen 1 normal embryonic and germ cell development in mice lacking 1,3-fucosyltransferase IX (Fut9) which show disappearance of stage-specific E, Mol. Cell. Biol., 24, 4221–4228, doi: 10.1128/MCB.24.10.4221.
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, doi: 10.1016/j.cub.2003.11.026.
35. Saitou, M., Kagiwada, S., and Kurimoto, K. (2012) Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells, Development, 139, 15–31, doi: 10.1242/dev.050849.
36. De Felici, M. (2009) Primordial germ cell biology at the beginning of the XXI century, Int. J. Dev. Biol., 53, 891–894, doi: 10.1387/ijdb.082815mf.
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, doi: 10.1038/11932.
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 establishment of the primitive streak in mice, Dev. Biol., 403, 80–88, doi: 10.1016/j.ydbio.2015.04.008.
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, doi: 10.1002/ar.1091170206.
40. Kellokumpu-Lehtinen, P.L., and Soderstrom, K.O. (1978) Occurrence of nuage in fetal human germ cells, Cell Tissue Res., 194, 171–177, doi: 10.1007/BF00209243.
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, doi: 10.1242/dev.00310.
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, P639–649.E6, doi: 10.1016/j.molcel.2018.04.009.
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 essential for spermatogenesis and transposon repression in meiosis, Dev. Cell., 15, 285–297, doi: 10.1016/j.devcel.2008.05.015.
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., 113, 201603813–201603817, doi: 10.1073/pnas.1603817113.
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, doi: 10.1016/j.stem.2016.01.017.
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, doi: 10.1634/stemcells.21-5-598.
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, doi: 10.1093/hmg/ddh088.
48. Tilgner, K., Atkinson, S.P., Golebiewska, A., Stojkovic, M., Lako, M., and Armstrong, L. (2008) Isolation of primordial germ cells from differentiating human embryonic stem cells, Stem Cells, 26, 3075–3085, doi: 10.1634/stemcells.2008-0289.
49. Kee, K., Gonsalves, J.M., Clark, A.T., and Pera, R.A. (2006) Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells, Stem Cells Dev., 15, 831–837, doi: 10.1089/scd.2006.15.831.
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, doi: 10.1126/science.1083452.
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, doi: 10.1038/nature02121.1.
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 significantly improved by coculture with human fetal gonadal cells, Stem Cells, 27, 783–795, doi: 10.1002/stem.13.
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, doi: 10.1093/hmg/ddq520.
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, doi: 10.1002/stem.672.
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-mediated 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, doi: 10.1186/s40001-014-0080-6.
56. Fujimoto, T., Miyayama, Y., and Fuyuta, M. (1977) The origin, migration and fine morphology of human primordial germ cells, Anat. Rec., 188, 315–329, doi: 10.1002/ar.1091880305.
57. Funkuda, T. (1976) Ultrastructure of primordial germ cells in human embryo, Virchows Archiv. B: Cell Pathology, 20, 85–89.
58. Castrillon, D.H., Quade, B.J., Wang, T.Y., Quigley, C., and Crum, C.P. (2000) The human VASA gene is specifically expressed in the germ cell lineage, Proc. Natl. Acad. Sci. USA, 97, 9585–9590, doi: 10.1073/pnas.160274797.
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, doi: 10.1002/stem.2422.
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, doi: 10.1093/humrep/dem411.
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, doi: 10.1634/stemcells.2007-0605.
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, doi: 10.1093/humrep/deu358.
63. Medrano, J.V., Ramathal, C., Nguyen, H.N., Simon, C., and Reijo Pera, R.A. (2012) Divergent RNA-binding proteins, DAZL and VASA, induce meiotic progression in human germ cells derived in vitro, Stem Cells, 30, 441–451, doi: 10.1002/stem.1012.
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 Reports, 10, 509–523, doi: 10.1016/j.stemcr.2018.01.001.
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 Reports, 2, 189–204, doi: 10.1016/j.stemcr.2013.12.009.
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, doi: 10.1016/j.fertnstert.2012.04.037.
67. Angeles Julaton, V.T., and Reijo Pera, R.A. (2011) NANOS3 function in human germ cell development, Hum. Mol. Genet., 20, 2238–2250, doi: 10.1093/hmg/ddr114.
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, doi: 10.1038/ncb2638.
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, doi: 10.1016/j.tig.2012.01.005.
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, doi: 10.1016/j.ydbio.2009.04.012.
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 development or upon in vitro culture, Biol. Reprod., 78, 852–858, doi: 10.1095/biolreprod.107.066175.
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 development and germ-cell malignancy, Nature, 460, 909–913, doi: 10.1038/nature08210.
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 Reports, 2, 440–446, doi: 10.1016/j.celrep.2012.07.015.
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, doi: 10.1038/nature12745.
75. Kilens, S., Meistermann, Di., Moreno, Di., 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.; Milieu Interieur Consortium (2018) Parallel derivation of isogenic human primed and naive induced pluripotent stem cells, Nat. Commun., 9, 1–13, doi: 10.1038/s41467-017-02107-w.
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, doi: 10.1016/j.stem.2016.06.011.
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, doi: 10.1073/pnas.1319738111.
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, doi: 10.1038/nbt1310.
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, doi: 10.1074/jbc.M111.338434.
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, doi: 10.15252/embj.201488049.
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 extraembryonic lineages, Cell Stem Cell, 9, 144–155, doi: 10.1016/j.stem.2011.06.015.
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, doi: 10.1016/j.devcel.2013.11.001.
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, doi: 10.1016/j.stem.2015.06.014.
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, doi: 10.1038/nature00927.
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, doi: 10.1016/j.stem.2012.12.012.
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, doi: 10.1016/j.scr.2017.04.005.
87. Singh, K., and Jaiswal, D. (2011) Human male infertility: a complex multifactorial phenotype, Reprod. Sci., 18, 418–425, doi: 10.1177/1933719111398148.
88. Bowles, J. (2006) Retinoid signaling determines germ cell fate in mice, Science, 312, 596–600, doi: 10.1126/science.1125691.
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, doi: 10.1210/en.2007-0492.
90. Abrao, M.S., Muzii, L., and Marana, R. (2013) Anatomical causes of female infertility and their management, Int. J. Gynecol. Obstet., 123, Suppl. 2, S18–S24, doi: 10.1016/j.ijgo.2013.09.008.
91. Anawalt, B.D. (2013) Approach to male infertility and induction of spermatogenesis, J. Clin. Endocrinol. Metab., 98, 3532–3542, doi: 10.1210/jc.2012-2400.
92. Rieger, D. (2012) Culture systems: physiological and environmental factors that can affect the outcome of human ART, Methods Mol. Biol., 912, 333–354, doi: 10.1007/978-1-61779-971-6_19.
93. Sharpe, R.M. (2010) Environmental/lifestyle effects on spermatogenesis, Philos. Trans. R Soc. Lond B Biol. Sci., 365, 1697–1712, doi: 10.1098/rstb.2009.0206.
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, doi: 10.1016/j.cell.2014.05.019.
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 endoderm differentiation in cooperation with Nanog, Stem Cells, 27, 1760–1771, doi: 10.1002/stem.110.
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, doi: 10.1634/stemcells.22-5-770.