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Semin Reprod Med 2017; 35(2): 139-146
DOI: 10.1055/s-0037-1599085
DOI: 10.1055/s-0037-1599085
Review Article
Of Mice and Men: In Vivo and In Vitro Studies of Primordial Germ Cell Specification
Further Information
Publication History
Publication Date:
09 March 2017 (online)
Abstract
Specification of mouse primordial germ cells (PGCs), the precursors of sperm and eggs, involves three major molecular events: repression of the somatic program, reacquisition of pluripotency, and reprogramming to a unique epigenetic ground state. Gene knockout studies in mouse models, along with global transcriptome analyses, have revealed the key signaling pathways and transcription factors essential for PGC specification. Knowledge obtained from these studies has been utilized extensively to develop robust in vitro PGC induction models not only in mice but also in humans. These models have, in turn, formed the basis for a detailed understanding of the signaling pathways and epigenetic dynamics during in vivo PGC specification and development. Recapitulation of human PGC specification in culture is of tremendous significance for understanding the mechanisms of human germ cell development in normal and disease states and has implications for addressing germ-cell–based causes of infertility.
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References
- 1 Extavour CG, Akam M. Mechanisms of germ cell specification across the metazoans: epigenesis and preformation. Development 2003; 130 (24) 5869-5884
- 2 Chatfield J, O'Reilly MA, Bachvarova RF , et al. Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos. Development 2014; 141 (12) 2429-2440
- 3 Ohinata Y, Ohta H, Shigeta M, Yamanaka K, Wakayama T, Saitou M. A signaling principle for the specification of the germ cell lineage in mice. Cell 2009; 137 (3) 571-584
- 4 Ewen-Campen B, Donoughe S, Clarke DN, Extavour CG. Germ cell specification requires zygotic mechanisms rather than germ plasm in a basally branching insect. Curr Biol 2013; 23 (10) 835-842
- 5 Ginsburg M, Snow MH, McLaren A. Primordial germ cells in the mouse embryo during gastrulation. Development 1990; 110 (2) 521-528
- 6 Lawson KA, Hage WJ. Clonal analysis of the origin of primordial germ cells in the mouse. Ciba Found Symp 1994; 182: 68-84 , discussion 84–91
- 7 Bowles J, Koopman P. Retinoic acid, meiosis and germ cell fate in mammals. Development 2007; 134 (19) 3401-3411
- 8 Tam PP, Loebel DA. Gene function in mouse embryogenesis: get set for gastrulation. Nat Rev Genet 2007; 8 (5) 368-381
- 9 Aramaki S, Hayashi K, Kurimoto K , et al. A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants. Dev Cell 2013; 27 (5) 516-529
- 10 Ying Y, Zhao GQ. Cooperation of endoderm-derived BMP2 and extraembryonic ectoderm-derived BMP4 in primordial germ cell generation in the mouse. Dev Biol 2001; 232 (2) 484-492
- 11 Lawson KA, Dunn NR, Roelen BA , et al. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 1999; 13 (4) 424-436
- 12 Ying Y, Liu XM, Marble A, Lawson KA, Zhao GQ. Requirement of Bmp8b for the generation of primordial germ cells in the mouse. Mol Endocrinol 2000; 14 (7) 1053-1063
- 13 Tremblay KD, Dunn NR, Robertson EJ. Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation. Development 2001; 128 (18) 3609-3621
- 14 Chu GC, Dunn NR, Anderson DC, Oxburgh L, Robertson EJ. Differential requirements for Smad4 in TGFbeta-dependent patterning of the early mouse embryo. Development 2004; 131 (15) 3501-3512
- 15 Chang H, Matzuk MM. Smad5 is required for mouse primordial germ cell development. Mech Dev 2001; 104 (01/02) 61-67
- 16 Ohinata Y, Payer B, O'Carroll D , et al. Blimp1 is a critical determinant of the germ cell lineage in mice. Nature 2005; 436 (7048): 207-213
- 17 Arnold SJ, Maretto S, Islam A, Bikoff EK, Robertson EJ. Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo. Dev Biol 2006; 296 (1) 104-118
- 18 Liu P, Wakamiya M, Shea MJ, Albrecht U, Behringer RR, Bradley A. Requirement for Wnt3 in vertebrate axis formation. Nat Genet 1999; 22 (4) 361-365
- 19 Brennan J, Lu CC, Norris DP, Rodriguez TA, Beddington RS, Robertson EJ. Nodal signalling in the epiblast patterns the early mouse embryo. Nature 2001; 411 (6840): 965-969
- 20 Vincent SD, Dunn NR, Sciammas R , et al. 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 2005; 132 (6) 1315-1325
- 21 Kurimoto K, Yabuta Y, Ohinata Y, Shigeta M, Yamanaka K, Saitou M. Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice. Genes Dev 2008; 22 (12) 1617-1635
- 22 Yamaji M, Seki Y, Kurimoto K , et al. Critical function of Prdm14 for the establishment of the germ cell lineage in mice. Nat Genet 2008; 40 (8) 1016-1022
- 23 Weber S, Eckert D, Nettersheim D , et al. Critical function of AP-2 gamma/TCFAP2C in mouse embryonic germ cell maintenance. Biol Reprod 2010; 82 (1) 214-223
- 24 Saitou M, Barton SC, Surani MA. A molecular programme for the specification of germ cell fate in mice. Nature 2002; 418 (6895): 293-300
- 25 Tang WW, Kobayashi T, Irie N, Dietmann S, Surani MA. Specification and epigenetic programming of the human germ line. Nat Rev Genet 2016; 17 (10) 585-600
- 26 Magnúsdóttir E, Dietmann S, Murakami K , et al. A tripartite transcription factor network regulates primordial germ cell specification in mice. Nat Cell Biol 2013; 15 (8) 905-915
- 27 Nakaki F, Hayashi K, Ohta H, Kurimoto K, Yabuta Y, Saitou M. Induction of mouse germ-cell fate by transcription factors in vitro. Nature 2013; 501 (7466): 222-226
- 28 Kurimoto K, Yabuta Y, Hayashi K , et al. Quantitative dynamics of chromatin remodeling during germ cell specification from mouse embryonic stem cells. Cell Stem Cell 2015; 16 (5) 517-532
- 29 Ma Z, Swigut T, Valouev A, Rada-Iglesias A, Wysocka J. Sequence-specific regulator Prdm14 safeguards mouse ESCs from entering extraembryonic endoderm fates. Nat Struct Mol Biol 2011; 18 (2) 120-127
- 30 Magnúsdóttir E, Surani MA. How to make a primordial germ cell. Development 2014; 141 (2) 245-252
- 31 Yamaji M, Ueda J, Hayashi K , et al. PRDM14 ensures naive pluripotency through dual regulation of signaling and epigenetic pathways in mouse embryonic stem cells. Cell Stem Cell 2013; 12 (3) 368-382
- 32 Tu S, Narendra V, Yamaji M , et al. Co-repressor CBFA2T2 regulates pluripotency and germline development. Nature 2016; 534 (7607): 387-390
- 33 Nady N, Gupta A, Ma Z , et al. ETO family protein Mtgr1 mediates Prdm14 functions in stem cell maintenance and primordial germ cell formation. eLife 2015; 4: e10150
- 34 Fog CK, Galli GG, Lund AH. PRDM proteins: important players in differentiation and disease. BioEssays 2012; 34 (1) 50-60
- 35 Kehler J, Tolkunova E, Koschorz B , et al. Oct4 is required for primordial germ cell survival. EMBO Rep 2004; 5 (11) 1078-1083
- 36 Yamaguchi S, Kurimoto K, Yabuta Y , et al. Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells. Development 2009; 136 (23) 4011-4020
- 37 Chambers I, Silva J, Colby D , et al. Nanog safeguards pluripotency and mediates germline development. Nature 2007; 450 (7173): 1230-1234
- 38 Campolo F, Gori M, Favaro R , et al. Essential role of Sox2 for the establishment and maintenance of the germ cell line. Stem Cells 2013; 31 (7) 1408-1421
- 39 Schöler HR, Dressler GR, Balling R, Rohdewohld H, Gruss P. Oct-4: a germline-specific transcription factor mapping to the mouse t-complex. EMBO J 1990; 9 (7) 2185-2195
- 40 Yeom YI, Fuhrmann G, Ovitt CE , et al. Germline regulatory element of Oct-4 specific for the totipotent cycle of embryonal cells. Development 1996; 122 (3) 881-894
- 41 Murakami K, Günesdogan U, Zylicz JJ , et al. NANOG alone induces germ cells in primed epiblast in vitro by activation of enhancers. Nature 2016; 529 (7586): 403-407
- 42 Saitou M, Kagiwada S, Kurimoto K. Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells. Development 2012; 139 (1) 15-31
- 43 Messerschmidt DM, Knowles BB, Solter D. DNA methylation dynamics during epigenetic reprogramming in the germline and preimplantation embryos. Genes Dev 2014; 28 (8) 812-828
- 44 Guibert S, Forné T, Weber M. Global profiling of DNA methylation erasure in mouse primordial germ cells. Genome Res 2012; 22 (4) 633-641
- 45 Sugimoto M, Abe K. X chromosome reactivation initiates in nascent primordial germ cells in mice. PLoS Genet 2007; 3 (7) e116
- 46 Chuva de Sousa Lopes SM, Hayashi K, Shovlin TC, Mifsud W, Surani MA, McLaren A. X chromosome activity in mouse XX primordial germ cells. PLoS Genet 2008; 4 (2) e30
- 47 Tam PP, Zhou SX, Tan SS. X-chromosome activity of the mouse primordial germ cells revealed by the expression of an X-linked lacZ transgene. Development 1994; 120 (10) 2925-2932
- 48 Monk M, McLaren A. X-chromosome activity in foetal germ cells of the mouse. J Embryol Exp Morphol 1981; 63: 75-84
- 49 Seisenberger S, Andrews S, Krueger F , et al. The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 2012; 48 (6) 849-862
- 50 Kobayashi H, Sakurai T, Miura F , et al. High-resolution DNA methylome analysis of primordial germ cells identifies gender-specific reprogramming in mice. Genome Res 2013; 23 (4) 616-627
- 51 Kagiwada S, Kurimoto K, Hirota T, Yamaji M, Saitou M. Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice. EMBO J 2013; 32 (3) 340-353
- 52 Ohno R, Nakayama M, Naruse C , et al. A replication-dependent passive mechanism modulates DNA demethylation in mouse primordial germ cells. Development 2013; 140 (14) 2892-2903
- 53 Arand J, Wossidlo M, Lepikhov K, Peat JR, Reik W, Walter J. Selective impairment of methylation maintenance is the major cause of DNA methylation reprogramming in the early embryo. Epigenetics Chromatin 2015; 8 (1) 1
- 54 Hackett JA, Sengupta R, Zylicz JJ , et al. Germline DNA demethylation dynamics and imprint erasure through 5-hydroxymethylcytosine. Science 2013; 339 (6118): 448-452
- 55 Hackett JA, Zylicz JJ, Surani MA. Parallel mechanisms of epigenetic reprogramming in the germline. Trends Genet 2012; 28 (4) 164-174
- 56 Yamaguchi S, Shen L, Liu Y, Sendler D, Zhang Y. Role of Tet1 in erasure of genomic imprinting. Nature 2013; 504 (7480): 460-464
- 57 Dawlaty MM, Breiling A, Le T , et al. Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development. Dev Cell 2013; 24 (3) 310-323
- 58 Yamaguchi S, Hong K, Liu R , et al. Tet1 controls meiosis by regulating meiotic gene expression. Nature 2012; 492 (7429): 443-447
- 59 Seki Y, Yamaji M, Yabuta Y , et al. Cellular dynamics associated with the genome-wide epigenetic reprogramming in migrating primordial germ cells in mice. Development 2007; 134 (14) 2627-2638
- 60 Seki Y, Hayashi K, Itoh K, Mizugaki M, Saitou M, Matsui Y. Extensive and orderly reprogramming of genome-wide chromatin modifications associated with specification and early development of germ cells in mice. Dev Biol 2005; 278 (2) 440-458
- 61 Saitou M, Yamaji M. Germ cell specification in mice: signaling, transcription regulation, and epigenetic consequences. Reproduction 2010; 139 (6) 931-942
- 62 Yabuta Y, Kurimoto K, Ohinata Y, Seki Y, Saitou M. Gene expression dynamics during germline specification in mice identified by quantitative single-cell gene expression profiling. Biol Reprod 2006; 75 (5) 705-716
- 63 Ancelin K, Lange UC, Hajkova P , et al. Blimp1 associates with Prmt5 and directs histone arginine methylation in mouse germ cells. Nat Cell Biol 2006; 8 (6) 623-630
- 64 Saitou M. Germ cell specification in mice. Curr Opin Genet Dev 2009; 19 (4) 386-395
- 65 Hübner K, Fuhrmann G, Christenson LK , et al. Derivation of oocytes from mouse embryonic stem cells. Science 2003; 300 (5623): 1251-1256
- 66 Toyooka Y, Tsunekawa N, Akasu R, Noce T. Embryonic stem cells can form germ cells in vitro. Proc Natl Acad Sci U S A 2003; 100 (20) 11457-11462
- 67 Geijsen N, Horoschak M, Kim K, Gribnau J, Eggan K, Daley GQ. Derivation of embryonic germ cells and male gametes from embryonic stem cells. Nature 2004; 427 (6970): 148-154
- 68 Nayernia K, Nolte J, Michelmann HW , et al. In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice. Dev Cell 2006; 11 (1) 125-132
- 69 Hayashi K, Surani MA. Self-renewing epiblast stem cells exhibit continual delineation of germ cells with epigenetic reprogramming in vitro. Development 2009; 136 (21) 3549-3556
- 70 Hayashi K, Ohta H, Kurimoto K, Aramaki S, Saitou M. Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell 2011; 146 (4) 519-532
- 71 Kee K, Gonsalves JM, Clark AT, Pera RA. Bone morphogenetic proteins induce germ cell differentiation from human embryonic stem cells. Stem Cells Dev 2006; 15 (6) 831-837
- 72 Kee K, Angeles VT, Flores M, Nguyen HN, Reijo Pera RA. Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature 2009; 462 (7270): 222-225
- 73 Clark AT, Bodnar MS, Fox M , et al. Spontaneous differentiation of germ cells from human embryonic stem cells in vitro. Hum Mol Genet 2004; 13 (7) 727-739
- 74 Irie N, Weinberger L, Tang WW , et al. SOX17 is a critical specifier of human primordial germ cell fate. Cell 2015; 160 (01/02) 253-268
- 75 Wu J, Izpisua Belmonte JC. Dynamic pluripotent stem cell states and their applications. Cell Stem Cell 2015; 17 (5) 509-525
- 76 Weinberger L, Ayyash M, Novershtern N, Hanna JH. Dynamic stem cell states: naive to primed pluripotency in rodents and humans. Nat Rev Mol Cell Biol 2016; 17 (3) 155-169
- 77 Gafni O, Weinberger L, Mansour AA , et al. Derivation of novel human ground state naive pluripotent stem cells. Nature 2013; 504 (7479): 282-286
- 78 Blakeley P, Fogarty NM, Del Valle I , et al. Defining the three cell lineages of the human blastocyst by single-cell RNA-seq. Development 2015; 142 (20) 3613
- 79 Pastor WA, Chen D, Liu W , et al. Naive human pluripotent cells feature a methylation landscape devoid of blastocyst or germline memory. Cell Stem Cell 2016; 18 (3) 323-329
- 80 Takashima Y, Guo G, Loos R , et al. Resetting transcription factor control circuitry toward ground-state pluripotency in human. Cell 2014; 158 (6) 1254-1269
- 81 Sasaki K, Yokobayashi S, Nakamura T , et al. Robust in vitro induction of human germ cell fate from pluripotent stem cells. Cell Stem Cell 2015; 17 (2) 178-194
- 82 Sugawa F, Araúzo-Bravo MJ, Yoon J , et al. Human primordial germ cell commitment in vitro associates with a unique PRDM14 expression profile. EMBO J 2015; 34 (8) 1009-1024