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Human Fertility pp 563–578Cite as

Human Germ Cell Differentiation from Pluripotent Embryonic Stem Cells and Induced Pluripotent Stem Cells

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1154))

Abstract

Although 10–15 % of couples are infertile, little is known of the diverse, underlying pathologies in men and women with poor germ cell production; furthermore, for those with few or no high-quality germ cells, there are few options available for treatment. Thus, over the last decade, concerted efforts have been aimed at developing a biological system to probe the fundamentals of human egg and sperm production via pluripotent stem cell cells with the hopes of informing clinical decisions and ultimately providing alternative methods for therapy which may include developing a source of germ cells ultimately for reproductive purposes.

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References

  1. Cedars M (2005) In: Cedars MI (ed) Infertility practical pathways in obstetrics and gynecology. McGraw-Hill, p xv–xviii

    Google Scholar 

  2. Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147

    Article  PubMed  CAS  Google Scholar 

  3. International Human Genome Sequencing Consortium (2001) Initial sequencing and analysis of the human genome. Nature 409:860–921

    Article  Google Scholar 

  4. Park I, Zhao R, West J, Yabuuchi A, Huo H, Ince T, Lerou P, Lensch M, Daley G (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146

    Article  PubMed  CAS  Google Scholar 

  5. Yu J, Vodyanik M, Smuga-Otto K, Antosiewicz-Bourget J, France J, Tian S, Nie J, Jonsdottir G, Ruotti V, Stewart R, Slukvin I, Thomson J (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  PubMed  CAS  Google Scholar 

  6. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  PubMed  CAS  Google Scholar 

  7. Reijo R, Alagappan RK, Patrizio P, Page DC (1996) Severe oligospermia resulting from deletions of the Azoospermia Factor gene on the Y chromosome. Lancet 347:1290–1293

    Article  PubMed  CAS  Google Scholar 

  8. Reijo R, Lee TY, Salo P, Alagappan R, Brown LG, Rosenberg M, Rozen S, Jaffe T, Straus D, Hovatta O et al (1995) Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet 10:383–393

    Article  PubMed  CAS  Google Scholar 

  9. Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, Kohn FM, Schill WB, Farah S, Ramos C, Hartmann M, Hartschuh W, Meschede D, Behre HM, Castel A, Nieschlag E, Weidner W, Grone H-J, Jung A, Engel W, Haidl G (1996) Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet 5:933–943

    Article  PubMed  CAS  Google Scholar 

  10. Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, Repping S, Pyntikova T, Ali J, Bieri T, Chinwalla A, Delehaunty A, Delehaunty K, Du H, Fewell G, Fulton L, Fulton R, Graves T, Hou SF, Latrielle P, Leonard S, Mardis E, Maupin R, McPherson J, Miner T, Nash W, Nguyen C, Ozersky P, Pepin K, Rock S, Rohlfing T, Scott K, Schultz B, Strong C, Tin-Wollam A, Yang SP, Waterston RH, Wilson RK, Rozen S, Page DC (2003) The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 423:825–837

    Article  PubMed  CAS  Google Scholar 

  11. Zinn AR, Page DC, Fisher EMC (1993) Turner syndrome: the case of the missing sex chromosome. Trends Genet 9:90–93

    Article  PubMed  CAS  Google Scholar 

  12. Hendry AP, Wenburg JK, Bentzen P, Volk EC, Quinn TP (2000) Rapid evolution of reproductive isolation in the wild: evidence from introduced salmon. Science 290:516–518

    Article  PubMed  CAS  Google Scholar 

  13. Swanson WJ, Vacquier VD (2002) The rapid evolution of reproductive proteins. Nat Rev Genet 3:137–144

    Article  PubMed  CAS  Google Scholar 

  14. Menken J, Larsen U (1994) Estimating the incidence and prevalence and analyzing the correlates of infertility and sterility. Ann N Y Acad Sci 709:249–265

    Article  PubMed  CAS  Google Scholar 

  15. Hunt PA, Hassold TJ (2002) Sex matters in meiosis. Science 296:2181–2183

    Article  PubMed  CAS  Google Scholar 

  16. Han J, Yuan P, Yang H, Zhang J, Soh B, Li P, Lim S, Cao S, Tay J, Orlov Y, Lufkin T, Ng H-H, Tam W-L, Lim B (2010) Tbx3 improves the germ-line competency of induced pluripotent stem cells. Nature 463:1096–1100

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  17. Matzuk M, Lamb D (2002) Genetic dissection of mammalian fertility pathways. Nat Cell Biol 4S:41–49

    Google Scholar 

  18. Fox MS, Clark AT, El Majdoubi M, Vigne JL, Urano J, Hostetler CE, Griswold MD, Weiner RI, Reijo Pera RA (2007) Intermolecular interactions of homologs of germ plasm components in mammalian germ cells. Dev Biol 301:417–431

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Jaruzelska J, Kotecki M, Kusz K, Spik A, Firpo M, Reijo RA (2003) Conservation of a Pumilio-Nanos complex from Drosophila germ plasm to human germ cells. Dev Genes Evol 213:120–126

    PubMed  CAS  Google Scholar 

  20. Houston DW, King ML (2000) Germ plasm and molecular determinants of germ cell fate. Curr Top Dev Biol 50:155–181

    Article  PubMed  CAS  Google Scholar 

  21. Lehmann R, Ephrussi A (1994) Germ plasm formation and germ cell determination in Drosophila. Ciba Found Symp 182:282–296

    PubMed  CAS  Google Scholar 

  22. Nicholas C, Chavez S, Baker V, Reijo Pera RA (2009) Instructing an embryonic stem cell-derived oocyte fate: lessons from endogenous oogenesis. Endocr Rev 30:264–283

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  23. Judson R, Babiarz J, Venere M, Blelloch R (2009) Embryonic stem cell-specific microRNAs promote induced pluripotency. Nat Biotechnol 27(5):459–461

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  24. Bucay N, Yebra M, Cirulli V, Afrikanova I, Kaido T, Hayek A, Montgomery A (2009) A novel approach for the derivation of putative primordial germ cells and Sertoli cells from human embryonic stem cells. Stem Cells 27: 68–77

    Article  PubMed  CAS  Google Scholar 

  25. Muller R, Lengerke C (2009) Patient-specific pluripotent stem cells: promises and challenges. Nat Rev Endocrinol 5:195–203

    Article  PubMed  Google Scholar 

  26. Kossack N, Meneses J, Shefi S, Nguyen H, Chavez S, Nicholas C, Gromoll J, Turek P, Reijo-Pera RA (2009) Isolation and characterization of pluripotent human spermatogonial stem cell-derived cells. Stem Cells 27:138–149

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Yu J, Thomson J (2008) Pluripotent stem cell lines. Genes Dev 22:1987–1997

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Kuroda-Kawaguchi T, Skaletsky H, Brown LG, Minx PJ, Cordum HS, Waterston RH, Wilson RK, Silber S, Oates R, Rozen S, Page DC (2001) The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet 29:279–286

    Article  PubMed  CAS  Google Scholar 

  29. Sun C, Skaletsky H, Rozen S, Gromoll J, Nieschlag E, Oates R, Page DC (2000) Deletion of azoospermia factor a (AZFa) region of human Y chromosome caused by recombination between HERV15 proviruses. Hum Mol Genet 9:2291–2296

    Article  PubMed  CAS  Google Scholar 

  30. Saxena R, Vries JW, Repping S, Alagappan RK, Skaletsky H, Brown LG, Ma P, Chen E, Hoovers JM, Page DC (2000) Four DAZ genes in two clusters found in the AZFc region of the human Y chromosome. Genomics 67: 256–267

    Article  PubMed  CAS  Google Scholar 

  31. Namiki M (2000) Genetic aspects of male infertility. World J Surg 24:1176–1179

    Article  PubMed  CAS  Google Scholar 

  32. Kee K, Angeles V, Flores M, Nguyen H, Reijo Pera RA (2009) Human DAZL, DAZ and BOULE genes modulate primordial germ cell and haploid gamete formation. Nature 462: 222–225

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  33. Kee K, Gonsalves J, Clark A, Reijo Pera RA (2006) Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells. Stem Cells Dev 15:831–837

    Article  PubMed  CAS  Google Scholar 

  34. Panula S, Medrano J, Kee K, Bergstrom R, Nguyen H, Byers B, Wilson K, Wu J, Simon C, Hovatta O, Reijo Pera RA (2010) Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells. Hum Mol Genet 20:752–762

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  35. Chavez S, Meneses J, Nguyen H, Kim S, Reijo Pera RA (2008) Characterization of six new human embryonic stem cell lines (HSF-7, -8, -9. -10, -12 and -13) derived in minimal animal-component conditions. Stem Cells Dev 17: 535–546

    Article  PubMed  CAS  Google Scholar 

  36. International Stem Cell Consortium (2007) Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. Nat Biotechnol 25:803–816

    Article  CAS  Google Scholar 

  37. Reijo-Pera R, Dejonge C, Bossert N, Yao M, Yang JH, Asadi N, Wong W, Wong C, Firpo M (2008) Gene expression profiles of human inner cell mass cells and embryonic stem cells. Differentiation 78:18–23

    Article  CAS  Google Scholar 

  38. Julaton V, Reijo Pera RA (2011) NANOS3 function in human germ cell development. Hum Mol Genet 20:2238–2250

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  39. Kee K, Flores M, Cedars M, Reijo Pera RA (2010) Human primordial germ cell formation is diminished by exposure to environmental toxicants acting through the AHR signaling pathway. Toxicol Sci 117:218–224

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  40. Clark AT, Bodnar MS, Fox MS, Rodriquez RT, Abeyta MJ, Firpo MT, Reijo Pera RA (2004) Spontaneous differentiation of germ cells from human embryonic stem cells in vitro. Hum Mol Genet 13:727–739

    Article  PubMed  CAS  Google Scholar 

  41. Clark AT, Rodriguez R, Bodnar M, Abeyta M, Turek P, Firpo M, Reijo RA (2004) Human STELLAR, NANOG, and GDF3 genes are expressed in pluripotent cells and map to chromosome 12p13, a hot-spot for teratocarcinoma. Stem Cells 22:169–179

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. CIPF & Fundación Instituto Valenciano de Infertilidad (FIVI), Valencia University, INCLIVA, Valencia, 46015, Spain

    Jose V. Medrano & Carlos Simon

  2. Department of Obstetrics and Gynecology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford University, Rm LK3C02, 3rd floor, Li Ka Shing Building, 291 Campus Drive, MC 5216, Stanford, CA, 94305-5463, USA

    Renee Reijo Pera

Authors
  1. Jose V. Medrano
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  2. Carlos Simon
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  3. Renee Reijo Pera
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Corresponding author

Correspondence to Renee Reijo Pera .

Editor information

Editors and Affiliations

  1. The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York, USA

    Zev Rosenwaks

  2. Dept. Developmental & Regenerative Biology, Ichan School of Medicine at Mount Sinai, New York, New York, USA

    Paul M. Wassarman

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Medrano, J.V., Simon, C., Pera, R.R. (2014). Human Germ Cell Differentiation from Pluripotent Embryonic Stem Cells and Induced Pluripotent Stem Cells. In: Rosenwaks, Z., Wassarman, P. (eds) Human Fertility. Methods in Molecular Biology, vol 1154. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0659-8_27

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  • DOI: https://doi.org/10.1007/978-1-4939-0659-8_27

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0658-1

  • Online ISBN: 978-1-4939-0659-8

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