Temporal Transcriptional Profiling of Somatic and Germ Cells Reveals Biased Lineage Priming of Sexual Fate in the Fetal Mouse Gonad
The divergence of distinct cell populations from multipotent progenitors is poorly understood, particularly in vivo. The gonad is an ideal place to study this process, because it originates as a bipotential primordium where multiple distinct lineages acquire sex-specific fates as the organ differentiates as a testis or an ovary. To gain a more detailed understanding of the process of gonadal differentiation at the level of the individual cell populations, we conducted microarrays on sorted cells from XX and XY mouse gonads at three time points spanning the period when the gonadal cells transition from sexually undifferentiated progenitors to their respective sex-specific fates. We analyzed supporting cells, interstitial/stromal cells, germ cells, and endothelial cells. This work identified genes specifically depleted and enriched in each lineage as it underwent sex-specific differentiation. We determined that the sexually undifferentiated germ cell and supporting cell progenitors showed lineage priming. We found that germ cell progenitors were primed with a bias toward the male fate. In contrast, supporting cells were primed with a female bias, indicative of the robust repression program involved in the commitment to XY supporting cell fate. This study provides a molecular explanation reconciling the female default and balanced models of sex determination and represents a rich resource for the field. More importantly, it yields new insights into the mechanisms by which different cell types in a single organ adopt their respective fates.
Vyšlo v časopise:
Temporal Transcriptional Profiling of Somatic and Germ Cells Reveals Biased Lineage Priming of Sexual Fate in the Fetal Mouse Gonad. PLoS Genet 8(3): e32767. doi:10.1371/journal.pgen.1002575
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002575
Souhrn
The divergence of distinct cell populations from multipotent progenitors is poorly understood, particularly in vivo. The gonad is an ideal place to study this process, because it originates as a bipotential primordium where multiple distinct lineages acquire sex-specific fates as the organ differentiates as a testis or an ovary. To gain a more detailed understanding of the process of gonadal differentiation at the level of the individual cell populations, we conducted microarrays on sorted cells from XX and XY mouse gonads at three time points spanning the period when the gonadal cells transition from sexually undifferentiated progenitors to their respective sex-specific fates. We analyzed supporting cells, interstitial/stromal cells, germ cells, and endothelial cells. This work identified genes specifically depleted and enriched in each lineage as it underwent sex-specific differentiation. We determined that the sexually undifferentiated germ cell and supporting cell progenitors showed lineage priming. We found that germ cell progenitors were primed with a bias toward the male fate. In contrast, supporting cells were primed with a female bias, indicative of the robust repression program involved in the commitment to XY supporting cell fate. This study provides a molecular explanation reconciling the female default and balanced models of sex determination and represents a rich resource for the field. More importantly, it yields new insights into the mechanisms by which different cell types in a single organ adopt their respective fates.
Zdroje
1. KoopmanPGubbayJVivianNGoodfellowPLovell-BadgeR 1991 Male development of chromosomally female mice transgenic for Sry. Nature 351 117 121
2. GubbayJCollignonJKoopmanPCapelBEconomouA 1990 A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature 346 245 250
3. KarlJCapelB 1998 Sertoli cells of the mouse testis originate from the coelomic epithelium. Dev Biol 203 323 333
4. WylieC 1999 Germ cells. Cell 96 165 174
5. CoveneyDCoolJOliverTCapelB 2008 Four-dimensional analysis of vascularization during primary development of an organ, the gonad. Proc Natl Acad Sci U S A 105 7212 7217
6. MartineauJNordqvistKTilmannCLovell-BadgeRCapelB 1997 Male-specific cell migration into the developing gonad. Curr Biol 7 958 968
7. AlbrechtKHEicherEM 2001 Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor. Dev Biol 240 92 107
8. AdamsIRMcLarenA 2002 Sexually dimorphic development of mouse primordial germ cells: switching from oogenesis to spermatogenesis. Development 129 1155 1164
9. SwainALovell-BadgeR 1999 Mammalian sex determination: a molecular drama. Genes Dev 13 755 767
10. BoumaGJHudsonQJWashburnLLEicherEM 2010 New candidate genes identified for controlling mouse gonadal sex determination and the early stages of granulosa and Sertoli cell differentiation. Biol Reprod 82 380 389
11. NefSSchaadOStallingsNRCederrothCRPitettiJL 2005 Gene expression during sex determination reveals a robust female genetic program at the onset of ovarian development. Dev Biol 287 361 377
12. MiseNFuchikamiTSugimotoMKobayakawaSIkeF 2008 Differences and similarities in the developmental status of embryo-derived stem cells and primordial germ cells revealed by global expression profiling. Genes Cells 13 863 877
13. BeverdamAKoopmanP 2006 Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes. Hum Mol Genet 15 417 431
14. RollandADLehmannKPJohnsonKJGaidoKWKoopmanP 2011 Uncovering gene regulatory networks during mouse fetal germ cell development. Biol Reprod 84 790 800
15. BoumaGJAffourtitJPBultCJEicherEM 2007 Transcriptional profile of mouse pre-granulosa and Sertoli cells isolated from early-differentiated fetal gonads. Gene Expr Patterns 7 113 123
16. BradySMOrlandoDALeeJYWangJYKochJ 2007 A high-resolution root spatiotemporal map reveals dominant expression patterns. Science 318 801 806
17. SaitouMBartonSCSuraniMA 2002 A molecular programme for the specification of germ cell fate in mice. Nature 418 293 300
18. BrunskillEWAronowBJGeorgasKRumballeBValeriusMT 2008 Atlas of gene expression in the developing kidney at microanatomic resolution. Dev Cell 15 781 791
19. JostA 1947 Recherches sur la diff'erenciation sexuelle de l'embryon de lapin. Arch Anat Microsc Morph Exp 271 315
20. McLarenA 1991 Development of the mammalian gonad: the fate of the supporting cell lineage. Bioessays 13 151 156
21. CapelB 1998 Sex in the 90s: SRY and the switch to the male pathway. Annu Rev Physiol 60 497 523
22. McElreaveyKVilainEAbbasNHerskowitzIFellousM 1993 A regulatory cascade hypothesis for mammalian sex determination: SRY represses a negative regulator of male development. Proc Natl Acad Sci U S A 90 3368 3372
23. EicherEMWashburnLL 1986 Genetic control of primary sex determination in mice. Annu Rev Genet 20 327 360
24. KimYKobayashiASekidoRDiNapoliLBrennanJ 2006 Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination. PLoS Biol 4 e187 doi:10.1371/journal.pbio.0040187
25. ChassotAARancFGregoireEPRoepers-GajadienHLTaketoMM 2008 Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary. Hum Mol Genet 17 1264 1277
26. SwainANarvaezVBurgoynePCamerinoGLovell-BadgeR 1998 Dax1 antagonizes Sry action in mammalian sex determination. Nature 391 761 767
27. MungerSCAylorDLSyedHAMagwenePMThreadgillDW 2009 Elucidation of the transcription network governing mammalian sex determination by exploiting strain-specific susceptibility to sex reversal. Genes Dev 23 2521 2536
28. DelormeBRingeJPontikoglouCGaillardJLangonneA 2009 Specific lineage-priming of bone marrow mesenchymal stem cells provides the molecular framework for their plasticity. Stem Cells 27 1142 1151
29. HuMKrauseDGreavesMSharkisSDexterM 1997 Multilineage gene expression precedes commitment in the hemopoietic system. Genes Dev 11 774 785
30. NgSYYoshidaTZhangJGeorgopoulosK 2009 Genome-wide lineage-specific transcriptional networks underscore Ikaros-dependent lymphoid priming in hematopoietic stem cells. Immunity 30 493 507
31. ZiporiD 2004 The nature of stem cells: state rather than entity. Nat Rev Genet 5 873 878
32. MiyamotoTIwasakiHReizisBYeMGrafT 2002 Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell 3 137 147
33. EnverTGreavesM 1998 Loops, lineage, and leukemia. Cell 94 9 12
34. HippJAHippJDAtalaASokerS 2010 Functional genomics: new insights into the ‘function’ of low levels of gene expression in stem cells. Curr Genomics 11 354 358
35. Golan-MashiachMDazardJEGerecht-NirSAmariglioNFisherT 2005 Design principle of gene expression used by human stem cells: implication for pluripotency. FASEB J 19 147 149
36. GuoGHussMTongGQWangCLi SunL 2010 Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst. Dev Cell 18 675 685
37. DietrichJEHiiragiT 2007 Stochastic patterning in the mouse pre-implantation embryo. Development 134 4219 4231
38. PlusaBPiliszekAFrankenbergSArtusJHadjantonakisAK 2008 Distinct sequential cell behaviours direct primitive endoderm formation in the mouse blastocyst. Development 135 3081 3091
39. KimYBinghamNSekidoRParkerKLLovell-BadgeR 2007 Fibroblast growth factor receptor 2 regulates proliferation and Sertoli differentiation during male sex determination. Proc Natl Acad Sci U S A 104 16558 16563
40. MoriguchiTHamadaMMoritoNTerunumaTHasegawaK 2006 MafB is essential for renal development and F4/80 expression in macrophages. Mol Cell Biol 26 5715 5727
41. DeFalcoTTakahashiSCapelB 2011 Two distinct origins for Leydig cell progenitors in the fetal testis. Dev Biol 352 14 26
42. SzaboPEHubnerKScholerHMannJR 2002 Allele-specific expression of imprinted genes in mouse migratory primordial germ cells. Mech Dev 115 157 160
43. LarinaIVShenWKellyOGHadjantonakisAKBaronMH 2009 A membrane associated mCherry fluorescent reporter line for studying vascular remodeling and cardiac function during murine embryonic development. Anat Rec (Hoboken) 292 333 341
44. PocheRALarinaIVScottMLSaikJEWestJL 2009 The Flk1-myr::mCherry mouse as a useful reporter to characterize multiple aspects of ocular blood vessel development and disease. Dev Dyn 238 2318 2326
45. CoolJCarmonaFDSzucsikJCCapelB 2008 Peritubular myoid cells are not the migrating population required for testis cord formation in the XY gonad. Sex Dev 2 128 133
46. SekidoRBarINarvaezVPennyGLovell-BadgeR 2004 SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors. Dev Biol 274 271 279
47. YaoHHAardemaJHolthusenK 2006 Sexually dimorphic regulation of inhibin beta B in establishing gonadal vasculature in mice. Biol Reprod 74 978 983
48. JeanesAWilhelmDWilsonMJBowlesJMcClivePJ 2005 Evaluation of candidate markers for the peritubular myoid cell lineage in the developing mouse testis. Reproduction 130 509 516
49. TsudaMSasaokaYKisoMAbeKHaraguchiS 2003 Conserved role of nanos proteins in germ cell development. Science 301 1239 1241
50. MenkeDBKoubovaJPageDC 2003 Sexual differentiation of germ cells in XX mouse gonads occurs in an anterior-to-posterior wave. Dev Biol 262 303 312
51. FongGHRossantJGertsensteinMBreitmanML 1995 Role of the Flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature 376 66 70
52. IkedaYShenWHIngrahamHAParkerKL 1994 Developmental expression of mouse steroidogenic factor-1, an essential regulator of the steroid hydroxylases. Mol Endocrinol 8 654 662
53. BeckervordersandforthRTripathiPNinkovicJBayamELepierA 2010 In vivo fate mapping and expression analysis reveals molecular hallmarks of prospectively isolated adult neural stem cells. Cell Stem Cell 7 744 758
54. FujikuraJYamatoEYonemuraSHosodaKMasuiS 2002 Differentiation of embryonic stem cells is induced by GATA factors. Genes Dev 16 784 789
55. HuberOKornRMcLaughlinJOhsugiMHerrmannBG 1996 Nuclear localization of beta-catenin by interaction with transcription factor LEF-1. Mech Dev 59 3 10
56. MaatoukDMDiNapoliLAlversAParkerKLTaketoMM 2008 Stabilization of beta-catenin in XY gonads causes male-to-female sex-reversal. Hum Mol Genet 17 2949 2955
57. SchmahlJEicherEMWashburnLLCapelB 2000 Sry induces cell proliferation in the mouse gonad. Development 127 65 73
58. MorkLMaatoukDMMcMahonJAGuoJJZhangP 2011 Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. Biol Reprod
59. BurgoynePSBuehrMKoopmanPRossantJMcLarenA 1988 Cell-autonomous action of the testis-determining gene: Sertoli cells are exclusively XY in XX----XY chimaeric mouse testes. Development 102 443 450
60. ManssonRHultquistALucSYangLAndersonK 2007 Molecular evidence for hierarchical transcriptional lineage priming in fetal and adult stem cells and multipotent progenitors. Immunity 26 407 419
61. RazE 2000 The function and regulation of vasa-like genes in germ-cell development. Genome Biol 1 REVIEWS1017
62. CookMSMungerSCNadeauJHCapelB 2011 Regulation of male germ cell cycle arrest and differentiation by DND1 is modulated by genetic background. Development 138 23 32
63. KentJWheatleySCAndrewsJESinclairAHKoopmanP 1996 A male-specific role for SOX9 in vertebrate sex determination. Development 122 2813 2822
64. Morais da SilvaSHackerAHarleyVGoodfellowPSwainA 1996 Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds. Nat Genet 14 62 68
65. BradfordSTHiramatsuRMaddugodaMPBernardPChaboissierMC 2009 The cerebellin 4 precursor gene is a direct target of SRY and SOX9 in mice. Biol Reprod 80 1178 1188
66. VainioSHeikkilaMKispertAChinNMcMahonAP 1999 Female development in mammals is regulated by Wnt-4 signalling. Nature 397 405 409
67. DavidsonEHRastJPOliveriPRansickACalestaniC 2002 A genomic regulatory network for development. Science 295 1669 1678
68. LarssonOScheeleCLiangZMollJKarlssonC 2004 Kinetics of senescence-associated changes of gene expression in an epithelial, temperature-sensitive SV40 large T antigen model. Cancer Res 64 482 489
69. BadieCItzhakiJESullivanMJCarpenterAJPorterAC 2000 Repression of CDK1 and other genes with CDE and CHR promoter elements during DNA damage-induced G(2)/M arrest in human cells. Mol Cell Biol 20 2358 2366
70. LasloPSpoonerCJWarmflashALanckiDWLeeHJ 2006 Multilineage transcriptional priming and determination of alternate hematopoietic cell fates. Cell 126 755 766
71. ParmaPRadiOVidalVChaboissierMCDellambraE 2006 R-spondin1 is essential in sex determination, skin differentiation and malignancy. Nat Genet 38 1304 1309
72. LiuCFBinghamNParkerKYaoHH 2009 Sex-specific roles of beta-catenin in mouse gonadal development. Hum Mol Genet 18 405 417
73. Jeays-WardKHoyleCBrennanJDandonneauMAlldusG 2003 Endothelial and steroidogenic cell migration are regulated by WNT4 in the developing mammalian gonad. Development 130 3663 3670
74. BernsteinBEMikkelsenTSXieXKamalMHuebertDJ 2006 A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125 315 326
75. MatsonCKMurphyMWSarverALGriswoldMDBardwellVJ 2011 DMRT1 prevents female reprogramming in the postnatal mammalian testis. Nature 476 101 104
76. RaymondCSMurphyMWO'SullivanMGBardwellVJZarkowerD 2000 Dmrt1, a gene related to worm and fly sexual regulators, is required for mammalian testis differentiation. Genes Dev 14 2587 2595
77. ChaboissierMCKobayashiAVidalVILutzkendorfSvan de KantHJ 2004 Functional analysis of Sox8 and Sox9 during sex determination in the mouse. Development 131 1891 1901
78. YaoHHMatzukMMJorgezCJMenkeDBPageDC 2004 Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis. Dev Dyn 230 210 215
79. VidalVPChaboissierMCde RooijDGSchedlA 2001 Sox9 induces testis development in XX transgenic mice. Nat Genet 28 216 217
80. EwenKAKoopmanP 2010 Mouse germ cell development: from specification to sex determination. Mol Cell Endocrinol 323 76 93
81. McLarenASoutheeD 1997 Entry of mouse embryonic germ cells into meiosis. Dev Biol 187 107 113
82. UpadhyaySZamboniL 1982 Ectopic germ cells: natural model for the study of germ cell sexual differentiation. Proc Natl Acad Sci U S A 79 6584 6588
83. ChumaSNakatsujiN 2001 Autonomous transition into meiosis of mouse fetal germ cells in vitro and its inhibition by gp130-mediated signaling. Dev Biol 229 468 479
84. FariniDScaldaferriMLIonaSLa SalaGDe FeliciM 2005 Growth factors sustain primordial germ cell survival, proliferation and entering into meiosis in the absence of somatic cells. Dev Biol 285 49 56
85. BowlesJKnightDSmithCWilhelmDRichmanJ 2006 Retinoid signaling determines germ cell fate in mice. Science 312 596 600
86. KumarSChatziCBradeTCunninghamTJZhaoX 2011 Sex-specific timing of meiotic initiation is regulated by Cyp26b1 independent of retinoic acid signalling. Nat Commun 2 151
87. KoubovaJMenkeDBZhouQCapelBGriswoldMD 2006 Retinoic acid regulates sex-specific timing of meiotic initiation in mice. Proc Natl Acad Sci U S A 103 2474 2479
88. ByskovAG 1974 Does the rete ovarii act as a trigger for the onset of meiosis? Nature 252 396 397
89. OWBakerTG 1976 Initiation and control of meiosis in hamster gonads in vitro. J Reprod Fertil 48 399 401
90. DiNapoliLBatchvarovJCapelB 2006 FGF9 promotes survival of germ cells in the fetal testis. Development 133 1519 1527
91. BowlesJFengCWSpillerCDavidsonTLJacksonA 2010 FGF9 suppresses meiosis and promotes male germ cell fate in mice. Dev Cell 19 440 449
92. BarriosFFilipponiDPellegriniMParonettoMPDi SienaS 2010 Opposing effects of retinoic acid and FGF9 on Nanos2 expression and meiotic entry of mouse germ cells. J Cell Sci 123 871 880
93. FrancavillaSZamboniL 1985 Differentiation of mouse ectopic germinal cells in intra- and perigonadal locations. J Exp Zool 233 101 109
94. BestDSahlenderDAWaltherNPedenAAAdamsIR 2008 Sdmg1 is a conserved transmembrane protein associated with germ cell sex determination and germline-soma interactions in mice. Development 135 1415 1425
95. PhillipsBTGasseiKOrwigKE 2010 Spermatogonial stem cell regulation and spermatogenesis. Philos Trans R Soc Lond B Biol Sci 365 1663 1678
96. ColvinJSGreenRPSchmahlJCapelBOrnitzDM 2001 Male-to-female sex reversal in mice lacking fibroblast growth factor 9. Cell 104 875 889
97. IdekerTGalitskiTHoodL 2001 A new approach to decoding life: systems biology. Annu Rev Genomics Hum Genet 2 343 372
98. BradySMZhangLMegrawMMartinezNJJiangE 2011 A stele-enriched gene regulatory network in the Arabidopsis root. Mol Syst Biol 7 459
99. BullejosMKoopmanP 2001 Spatially dynamic expression of Sry in mouse genital ridges. Dev Dyn 221 201 205
100. SekidoRLovell-BadgeR 2008 Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 453 930 934
101. MrozKCarrelLHuntPA 1999 Germ cell development in the XXY mouse: evidence that X chromosome reactivation is independent of sexual differentiation. Dev Biol 207 229 238
102. CookMSCoveneyDBatchvarovINadeauJHCapelB 2009 BAX-mediated cell death affects early germ cell loss and incidence of testicular teratomas in Dnd1(Ter/Ter) mice. Dev Biol 328 377 383
103. BarskeLACapelB 2010 Estrogen represses SOX9 during sex determination in the red-eared slider turtle Trachemys scripta. Dev Biol 341 305 314
104. Huang daWShermanBTLempickiRA 2009 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4 44 57
105. Huang daWShermanBTLempickiRA 2009 Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37 1 13
106. LiuGLoraineAEShigetaRClineMChengJ 2003 NetAffx: Affymetrix probesets and annotations. Nucleic Acids Res 31 82 86
107. JhoEHZhangTDomonCJooCKFreundJN 2002 Wnt/beta-catenin/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 22 1172 1183
108. JorgensenJSGaoL 2005 Irx3 is differentially up-regulated in female gonads during sex determination. Gene Expr Patterns 5 756 762
109. CoveneyDRossAJSloneJDCapelB 2008 A microarray analysis of the XX Wnt4 mutant gonad targeted at the identification of genes involved in testis vascular differentiation. Gene Expr Patterns 8 529 537
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2012 Číslo 3
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- PIF4–Mediated Activation of Expression Integrates Temperature into the Auxin Pathway in Regulating Hypocotyl Growth
- Metabolic Profiling of a Mapping Population Exposes New Insights in the Regulation of Seed Metabolism and Seed, Fruit, and Plant Relations
- Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database
- Networks of Neuronal Genes Affected by Common and Rare Variants in Autism Spectrum Disorders