1932

Abstract

Spermatogenesis is a complex differentiation process coordinated spatiotemporally across and along seminiferous tubules. Cellular heterogeneity has made it challenging to obtain stage-specific molecular profiles of germ and somatic cells using bulk transcriptomic analyses. This has limited our ability to understand regulation of spermatogenesis and to integrate knowledge from model organisms to humans. The recent advancement of single-cell RNA-sequencing (scRNA-seq) technologies provides insights into the cell type diversity and molecular signatures in the testis. Fine-grained cell atlases of the testis contain both known and novel cell types and define the functional states along the germ cell developmental trajectory in many species. These atlases provide a reference system for integrated interspecies comparisons to discover mechanistic parallels and to enable future studies. Despite recent advances, we currently lack high-resolution data to probe germ cell–somatic cell interactions in the tissue environment, but the use of highly multiplexed spatial analysis technologies has begun to resolve this problem. Taken together, recent single-cell studies provide an improvedunderstanding of gametogenesis to examine underlying causes of infertility and enable the development of new therapeutic interventions.

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2022-11-30
2024-04-29
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Literature Cited

  1. 1.
    Aramaki S, Hayashi K, Kurimoto K, Ohta H, Yabuta Y et al. 2013. A mesodermal factor, T, specifies mouse germ cell fate by directly activating germline determinants. Dev. Cell 27:516–29
    [Google Scholar]
  2. 2.
    Aravin AA, Hannon GJ, Brennecke J. 2007. The Piwi-piRNA pathway provides an adaptive defense in the transposon arms race. Science 318:761–64
    [Google Scholar]
  3. 3.
    Aravin AA, Sachidanandam R, Bourc'his D, Schaefer C, Pezic D et al. 2008. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol. Cell 31:785–99
    [Google Scholar]
  4. 4.
    Ball RL, Fujiwara Y, Sun F, Hu J, Hibbs MA et al. 2016. Regulatory complexity revealed by integrated cytological and RNA-seq analyses of meiotic substages in mouse spermatocytes. BMC Genom. 17:628
    [Google Scholar]
  5. 5.
    Barau J, Teissandier A, Zamudio N, Roy S, Nalesso V et al. 2016. The DNA methyltransferase DNMT3C protects male germ cells from transposon activity. Science 354:909–12
    [Google Scholar]
  6. 6.
    Bellve AR. 1993. Purification, culture, and fractionation of spermatogenic cells. Methods Enzymol. 225:84–113
    [Google Scholar]
  7. 7.
    Borg CL, Wolski KM, Gibbs GM, O'Bryan MK. 2010. Phenotyping male infertility in the mouse: how to get the most out of a ‘non-performer. .’ Hum. Reprod. Update 16:205–24
    [Google Scholar]
  8. 8.
    Bose S, Wan Z, Carr A, Rizvi AH, Vieira G et al. 2015. Scalable microfluidics for single-cell RNA printing and sequencing. Genome Biol 16:120
    [Google Scholar]
  9. 9.
    Bourc'his D, Bestor TH 2004. Meiotic catastrophe and retrotransposon reactivation in male germ cells lacking Dnmt3L. Nature 431:96–99
    [Google Scholar]
  10. 10.
    Bourc'his D, Xu GL, Lin CS, Bollman B, Bestor TH. 2001. Dnmt3L and the establishment of maternal genomic imprints. Science 294:2536–39
    [Google Scholar]
  11. 11.
    Brawand D, Soumillon M, Necsulea A, Julien P, Csárdi G et al. 2011. The evolution of gene expression levels in mammalian organs. Nature 478:343–48
    [Google Scholar]
  12. 12.
    Broering TJ, Alavattam KG, Sadreyev RI, Ichijima Y, Kato Y et al. 2014. BRCA1 establishes DNA damage signaling and pericentric heterochromatin of the X chromosome in male meiosis. J. Cell Biol. 205:663–75
    [Google Scholar]
  13. 13.
    Budnik B, Levy E, Harmange G, Slavov N. 2018. SCoPE-MS: mass spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation. Genome Biol. 19:161
    [Google Scholar]
  14. 14.
    Cardoso-Moreira M, Halbert J, Valloton D, Velten B, Chen C et al. 2019. Gene expression across mammalian organ development. Nature 571:505–9
    [Google Scholar]
  15. 15.
    Carmell MA, Girard A, van de Kant HJG, Bourc'his D, Bestor TH et al. 2007. MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev. Cell 12:503–14
    [Google Scholar]
  16. 16.
    Chan F, Oatley MJ, Kaucher AV, Yang Q-E, Bieberich CJ et al. 2014. Functional and molecular features of the Id4+ germline stem cell population in mouse testes. Genes Dev. 28:1351–62
    [Google Scholar]
  17. 17.
    Chen H, Murray E, Sinha A, Laumas A, Li J et al. 2021. Dissecting mammalian spermatogenesis using spatial transcriptomics. Cell Rep. 37:109915
    [Google Scholar]
  18. 18.
    Chen S, Zhang YE, Long M. 2010. New genes in Drosophila quickly become essential. Science 330:1682–85
    [Google Scholar]
  19. 19.
    Chen X, Zhang J. 2014. Yeast mutation accumulation experiment supports elevated mutation rates at highly transcribed sites. PNAS 111:E4062
    [Google Scholar]
  20. 20.
    Chen Y, Zheng Y, Gao Y, Lin Z, Yang S et al. 2018. Single-cell RNA-seq uncovers dynamic processes and critical regulators in mouse spermatogenesis. Cell Res. 28:879–96
    [Google Scholar]
  21. 21.
    Chiarini-Garcia H, Hornick JR, Griswold MD, Russell LD. 2001. Distribution of type A spermatogonia in the mouse is not random. Biol. Reprod. 65:1179–85
    [Google Scholar]
  22. 22.
    Chiarini-Garcia H, Raymer AM, Russell LD. 2003. Non-random distribution of spermatogonia in rats: evidence of niches in the seminiferous tubules. Reproduction 126:669–80
    [Google Scholar]
  23. 23.
    Cho C-S, Xi J, Si Y, Park S-R, Hsu J-E et al. 2021. Microscopic examination of spatial transcriptome using Seq-Scope. Cell 184:3559–72.e22
    [Google Scholar]
  24. 24.
    Clark AM, Garland KK, Russell LD. 2000. Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules. Biol. Reprod. 63:1825–38
    [Google Scholar]
  25. 25.
    Clark MB, Amaral PP, Schlesinger FJ, Dinger ME, Taft RJ et al. 2011. The reality of pervasive transcription. PLOS Biol. 9:e1000625
    [Google Scholar]
  26. 26.
    Clermont Y. 1966. Renewal of spermatogonia in man. Am. J. Anat. 118:509–24
    [Google Scholar]
  27. 27.
    Clermont Y. 1966. Spermatogenesis in man. A study of the spermatogonial population. Fertil. Steril. 17:705–21
    [Google Scholar]
  28. 28.
    Clermont Y. 1969. Two classes of spermatogonial stem cells in the monkey (Cercopithecus aethiops). Am. J. Anat. 126:57–71
    [Google Scholar]
  29. 29.
    Clermont Y. 1972. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol. Rev. 52:198–236
    [Google Scholar]
  30. 30.
    Clermont Y, Antar M. 1973. Duration of the cycle of the seminiferous epithelium and the spermatogonial renewal in the monkey Macaca arctoides. Am. J. Anat. 136:153–65
    [Google Scholar]
  31. 31.
    Clermont Y, Leblond CP. 1959. Differentiation and renewal of spermatogonia in the monkey, Macacus rhesus. Am. J. Anat. 104:237–73
    [Google Scholar]
  32. 32.
    Clouthier DE, Avarbock MR, Maika SD, Hammer RE, Brinster RL. 1996. Rat spermatogenesis in mouse testis. Nature 381:418–21
    [Google Scholar]
  33. 33.
    Craig JR, Jenkins TG, Carrell DT, Hotaling JM. 2017. Obesity, male infertility, and the sperm epigenome. Fertil. Steril. 107:848–59
    [Google Scholar]
  34. 34.
    da Cruz I, Rodríguez-Casuriaga R, Santiñaque FF, Farías J, Curti G et al. 2016. Transcriptome analysis of highly purified mouse spermatogenic cell populations: gene expression signatures switch from meiotic-to postmeiotic-related processes at pachytene stage. BMC Genom. 17:294
    [Google Scholar]
  35. 35.
    Danielian PS, Hess RA, Lees JA. 2016. E2f4 and E2f5 are essential for the development of the male reproductive system. Cell Cycle 15:250–60
    [Google Scholar]
  36. 36.
    de Rooij DG. 1973. Spermatogonial stem cell renewal in the mouse: I. Normal situation. Cell Prolif. 6:281–87
    [Google Scholar]
  37. 37.
    de Rooij DG, van Alphen MM, van de Kant HJ. 1986. Duration of the cycle of the seminiferous epithelium and its stages in the rhesus monkey (Macaca mulatta). Biol. Reprod. 35:587–91
    [Google Scholar]
  38. 38.
    DeFalco T, Potter SJ, Williams AV, Waller B, Kan MJ, Capel B. 2015. Macrophages contribute to the spermatogonial niche in the adult testis. Cell Rep 12:1107–19
    [Google Scholar]
  39. 39.
    Dias BG, Ressler KJ. 2014. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat. Neurosci. 17:89–96
    [Google Scholar]
  40. 40.
    Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T et al. 2012. Landscape of transcription in human cells. Nature 489:101–8
    [Google Scholar]
  41. 41.
    Eng CL, Lawson M, Zhu Q, Dries R, Koulena N et al. 2019. Transcriptome-scale super-resolved imaging in tissues by RNA seqFISH. Nature 568:235–39
    [Google Scholar]
  42. 42.
    Ernst C, Eling N, Martinez-Jimenez CP, Marioni JC, Odom DT. 2019. Staged developmental mapping and X chromosome transcriptional dynamics during mouse spermatogenesis. Nat. Commun. 10:1251
    [Google Scholar]
  43. 43.
    Evans E, Hogarth C, Mitchell D, Griswold M 2014. Riding the spermatogenic wave: profiling gene expression within neonatal germ and Sertoli cells during a synchronized initial wave of spermatogenesis in mice. Biol. Reprod. 90:108
    [Google Scholar]
  44. 44.
    Fan HC, Fu GK, Fodor SP. 2015. Expression profiling. Combinatorial labeling of single cells for gene expression cytometry. Science 347:1258367
    [Google Scholar]
  45. 45.
    Fayomi AP, Orwig KE. 2018. Spermatogonial stem cells and spermatogenesis in mice, monkeys and men. Stem. Cell Res. 29:207–14
    [Google Scholar]
  46. 46.
    Fouquet JP, Dadoune JP. 1986. Renewal of spermatogonia in the monkey (Macaca fascicularis). Biol. Reprod. 35:199–207
    [Google Scholar]
  47. 47.
    Franca LR, Ogawa T, Avarbock MR, Brinster RL, Russell LD. 1998. Germ cell genotype controls cell cycle during spermatogenesis in the rat. Biol. Reprod. 59:1371–77
    [Google Scholar]
  48. 48.
    Fu X, Sun L, Chen JY, Dong R, Lin Y et al. 2021. Continuous polony gels for tissue mapping with high resolution and RNA capture efficiency. bioRxiv 2021.03.17.435795. https://doi.org/10.1101/2021.03.17.435795
    [Crossref]
  49. 49.
    Fukuda N, Fukuda T, Sinnamon J, Hernandez-Hernandez A, Izadi M et al. 2013. The transacting factor CBF-A/Hnrnpab binds to the A2RE/RTS element of protamine 2 mRNA and contributes to its translational regulation during mouse spermatogenesis. PLOS Genet. 9:e1003858
    [Google Scholar]
  50. 50.
    Garcia-Alonso L, Lorenzi V, Mazzeo CI, Alves-Lopes JP, Roberts K et al. 2022. Single-cell roadmap of human gonadal development. Nature 607:7919540–47
    [Google Scholar]
  51. 51.
    Gassei K, Orwig KE. 2016. Experimental methods to preserve male fertility and treat male factor infertility. Fertil. Steril. 105:256–66
    [Google Scholar]
  52. 52.
    Ge RS, Dong Q, Sottas CM, Chen H, Zirkin BR, Hardy MP. 2005. Gene expression in rat Leydig cells during development from the progenitor to adult stage: a cluster analysis. Biol. Reprod. 72:1405–15
    [Google Scholar]
  53. 53.
    Gill ME, Hu YC, Lin Y, Page DC. 2011. Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells. PNAS 108:7443–48
    [Google Scholar]
  54. 54.
    Gkountela S, Zhang KX, Shafiq TA, Liao WW, Hargan-Calvopina J et al. 2015. DNA demethylation dynamics in the human prenatal germline. Cell 161:1425–36
    [Google Scholar]
  55. 55.
    Green CD, Ma Q, Manske GL, Shami AN, Zheng X et al. 2018. A comprehensive roadmap of murine spermatogenesis defined by single-cell RNA-seq. Dev. Cell 46:651–67.e10
    [Google Scholar]
  56. 56.
    Griswold MD. 2016. Spermatogenesis: the commitment to meiosis. Physiol. Rev. 96:1–17
    [Google Scholar]
  57. 57.
    Grive KJ, Hu Y, Shu E, Grimson A, Elemento O et al. 2019. Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing. PLOS Genet 15:e1007810
    [Google Scholar]
  58. 58.
    Grivna ST, Pyhtila B, Lin H. 2006. MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis. PNAS 103:13415–20
    [Google Scholar]
  59. 59.
    Guo F, Yan L, Guo H, Li L, Hu B et al. 2015. The transcriptome and DNA methylome landscapes of human primordial germ cells. Cell 161:1437–52
    [Google Scholar]
  60. 60.
    Guo J, Grow EJ, Mlcochova H, Maher GJ, Lindskog C et al. 2018. The adult human testis transcriptional cell atlas. Cell Res 28:1141–57
    [Google Scholar]
  61. 61.
    Guo J, Grow EJ, Yi C, Mlcochova H, Maher GJ et al. 2017. Chromatin and single-cell RNA-seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development. Cell Stem Cell 21:533–46.e6
    [Google Scholar]
  62. 62.
    Guo J, Nie X, Giebler M, Mlcochova H, Wang Y et al. 2020. The dynamic transcriptional cell atlas of testis development during human puberty. Cell Stem Cell 26:262–76.e4
    [Google Scholar]
  63. 63.
    Guo J, Sosa E, Chitiashvili T, Nie X, Rojas EJ et al. 2021. Single-cell analysis of the developing human testis reveals somatic niche cell specification and fetal germline stem cell establishment. Cell Stem Cell 28:764–78.e4
    [Google Scholar]
  64. 64.
    Haaf T, Golub EI, Reddy G, Radding CM, Ward DC. 1995. Nuclear foci of mammalian Rad51 recombination protein in somatic cells after DNA damage and its localization in synaptonemal complexes. PNAS 92:2298–302
    [Google Scholar]
  65. 65.
    Hammoud SS, Low DH, Yi C, Carrell DT, Guccione E, Cairns BR. 2014. Chromatin and transcription transitions of mammalian adult germline stem cells and spermatogenesis. Cell Stem Cell 15:239–53
    [Google Scholar]
  66. 66.
    Hammoud SS, Low DH, Yi C, Lee CL, Oatley JM et al. 2015. Transcription and imprinting dynamics in developing postnatal male germline stem cells. Genes Dev. 29:2312–24
    [Google Scholar]
  67. 67.
    Hamra FK, Chapman KM, Nguyen DM, Williams-Stephens AA, Hammer RE, Garbers DL. 2005. Self renewal, expansion, and transfection of rat spermatogonial stem cells in culture. PNAS 102:17430–35
    [Google Scholar]
  68. 68.
    Hara K, Nakagawa T, Enomoto H, Suzuki M, Yamamoto M et al. 2014. Mouse spermatogenic stem cells continually interconvert between equipotent singly isolated and syncytial states. Cell Stem Cell 14:658–72
    [Google Scholar]
  69. 69.
    Harcourt AH, Harvey PH, Larson SG, Short RV. 1981. Testis weight, body weight and breeding system in primates. Nature 293:55–57
    [Google Scholar]
  70. 70.
    Hasegawa K, Saga Y. 2012. Retinoic acid signaling in Sertoli cells regulates organization of the blood-testis barrier through cyclical changes in gene expression. Development 139:4347–55
    [Google Scholar]
  71. 71.
    Hashimshony T, Wagner F, Sher N, Yanai I 2012. CEL-Seq: single-cell RNA-Seq by multiplexed linear amplification. Cell Rep. 2:666–73
    [Google Scholar]
  72. 72.
    Hayashi K, Saitou M. 2014. Perspectives of germ cell development in vitro in mammals. Anim. Sci. J. 85:617–26
    [Google Scholar]
  73. 73.
    Hayashi Y, Saitou M, Yamanaka S. 2012. Germline development from human pluripotent stem cells toward disease modeling of infertility. Fertil. Steril. 97:1250–59
    [Google Scholar]
  74. 74.
    He S, Bhatt R, Birditt B, Brown C, Brown E et al. 2021. High-plex multiomic analysis in FFPE tissue at single-cellular and subcellular resolution by spatial molecular imaging. bioRxiv 2021.11.03.467020. https://doi.org/10.1101/2021.11.03.467020
    [Crossref]
  75. 75.
    Heller CH, Clermont Y. 1964. Kinetics of the germinal epithelium in man. Recent. Prog. Horm. Res. 20:545–75
    [Google Scholar]
  76. 76.
    Heller CG, Heller GV, Rowley MJ. 1969. Human spermatogenesis: an estimate of the duration of each cell association and of each cell type. Excerpta Med. Found. Intern. Congr. Ser. 184:1012–18
    [Google Scholar]
  77. 77.
    Hermann BP, Cheng K, Singh A, Roa-De La Cruz L, Mutoji KN et al. 2018. The mammalian spermatogenesis single-cell transcriptome, from spermatogonial stem cells to spermatids. Cell Rep. 25:1650–67.e8
    [Google Scholar]
  78. 78.
    Hermann BP, Mutoji KN, Velte EK, Ko D, Oatley JM et al. 2015. Transcriptional and translational heterogeneity among neonatal mouse spermatogonia. Biol. Reprod. 92:54
    [Google Scholar]
  79. 79.
    Hermann BP, Sukhwani M, Simorangkir DR, Chu T, Plant TM, Orwig KE. 2009. Molecular dissection of the male germ cell lineage identifies putative spermatogonial stem cells in rhesus macaques. Hum. Reprod. 24:1704–16
    [Google Scholar]
  80. 80.
    Houston BJ, Conrad DF, O'Bryan MK. 2021. A framework for high-resolution phenotyping of candidate male infertility mutants: from human to mouse. Hum. Genet. 140:155–82
    [Google Scholar]
  81. 81.
    Houston BJ, Riera-Escamilla A, Wyrwoll MJ, Salas-Huetos A, Xavier MJ et al. 2021. A systematic review of the validated monogenic causes of human male infertility: 2020 update and a discussion of emerging gene–disease relationships. Hum. Reprod. Update 28:15–29
    [Google Scholar]
  82. 82.
    Huang T, Yuan S, Gao L, Li M, Yu X et al. 2020. The histone modification reader ZCWPW1 links histone methylation to PRDM9-induced double-strand break repair. eLife 9:e53459
    [Google Scholar]
  83. 83.
    Huckins C. 1971. The spermatogonial stem cell population in adult rats. I. Their morphology, proliferation and maturation. Anat. Rec. 169:533–57
    [Google Scholar]
  84. 84.
    Huckins C. 1978. The morphology and kinetics of spermatogonial degeneration in normal adult rats: an analysis using a simplified classification of the germinal epithelium. Anat. Rec. 190:905–26
    [Google Scholar]
  85. 85.
    Huckins C, Oakberg EF. 1978. Morphological and quantitative analysis of spermatogonia in mouse testes using whole mounted seminiferous tubules, I. The normal testes. Anat. Rec. 192:519–28
    [Google Scholar]
  86. 86.
    Hwang B, Lee JH, Bang D. 2018. Single-cell RNA sequencing technologies and bioinformatics pipelines. Exp. Mol. Med. 50:96
    [Google Scholar]
  87. 87.
    Hwang K, Yatsenko AN, Jorgez CJ, Mukherjee S, Nalam RL et al. 2010. Mendelian genetics of male infertility. Ann. N. Y. Acad. Sci. 1214:E1–17
    [Google Scholar]
  88. 88.
    Irie N, Surani MA. 2017. Efficient induction and isolation of human primordial germ cell-like cells from competent human pluripotent stem cells. Methods Mol. Biol. 1463:217–26
    [Google Scholar]
  89. 89.
    Irie N, Weinberger L, Tang WW, Kobayashi T, Viukov S et al. 2015. SOX17 is a critical specifier of human primordial germ cell fate. Cell 160:253–68
    [Google Scholar]
  90. 90.
    Islam S, Zeisel A, Joost S, La Manno G, Zajac P et al. 2014. Quantitative single-cell RNA-seq with unique molecular identifiers. Nat. Methods 11:163–66
    [Google Scholar]
  91. 91.
    Jan SZ, Vormer TL, Jongejan A, Roling MD, Silber SJ et al. 2017. Unraveling transcriptome dynamics in human spermatogenesis. Development 144:3659–73
    [Google Scholar]
  92. 92.
    Jauregui EJ, Mitchell D, Garza SM, Topping T, Hogarth CA, Griswold MD. 2018. Leydig cell genes change their expression and association with polysomes in a stage-specific manner in the adult mouse testis. Biol. Reprod. 98:722–38
    [Google Scholar]
  93. 93.
    Jinks-Robertson S, Bhagwat AS. 2014. Transcription-associated mutagenesis. Annu. Rev. Genet. 48:341–59
    [Google Scholar]
  94. 94.
    Johnston DS, Wright WW, Dicandeloro P, Wilson E, Kopf GS, Jelinsky SA. 2008. Stage-specific gene expression is a fundamental characteristic of rat spermatogenic cells and Sertoli cells. PNAS 105:8315–20
    [Google Scholar]
  95. 95.
    Jung M, Wells D, Rusch J, Ahmad S, Marchini J et al. 2019. Unified single-cell analysis of testis gene regulation and pathology in five mouse strains. eLife 8:e43966
    [Google Scholar]
  96. 96.
    Kafri T, Ariel M, Brandeis M, Shemer R, Urven L et al. 1992. Developmental pattern of gene-specific DNA methylation in the mouse embryo and germ line. Genes Dev. 6:705–14
    [Google Scholar]
  97. 97.
    Kanatsu-Shinohara M, Ogonuki N, Inoue K, Miki H, Ogura A et al. 2003. Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biol. Reprod. 69:612–16
    [Google Scholar]
  98. 98.
    Kerr JB. 1988. A light microscopic and morphometric analysis of the Sertoli cell during the spermatogenic cycle of the rat. Anat. Embryol. 177:341–48
    [Google Scholar]
  99. 99.
    Kerr JB. 1988. An ultrastructural and morphometric analysis of the Sertoli cell during the spermatogenic cycle of the rat. Anat. Embryol. 179:191–203
    [Google Scholar]
  100. 100.
    Kitadate Y, Jorg DJ, Tokue M, Maruyama A, Ichikawa R et al. 2019. Competition for mitogens regulates spermatogenic stem cell homeostasis in an open niche. Cell Stem Cell 24:79–92.e6
    [Google Scholar]
  101. 101.
    Kleene KC. 1996. Patterns of translational regulation in the mammalian testis. Mol. Reprod. Dev. 43:268–81
    [Google Scholar]
  102. 102.
    Kleene KC. 2001. A possible meiotic function of the peculiar patterns of gene expression in mammalian spermatogenic cells. Mech. Dev. 106:3–23
    [Google Scholar]
  103. 103.
    Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A et al. 2015. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161:1187–201
    [Google Scholar]
  104. 104.
    Kliesch S, Penttila TL, Gromoll J, Saunders PT, Nieschlag E, Parvinen M. 1992. FSH receptor mRNA is expressed stage-dependently during rat spermatogenesis. Mol. Cell. Endocrinol. 84:R45–49
    [Google Scholar]
  105. 105.
    Kobayashi T, Surani MA. 2018. On the origin of the human germline. Development 145:dev150433
    [Google Scholar]
  106. 106.
    Kobayashi T, Zhang H, Tang WWC, Irie N, Withey S et al. 2017. Principles of early human development and germ cell program from conserved model systems. Nature 546:416–20
    [Google Scholar]
  107. 107.
    Kojima Y, Sasaki K, Yokobayashi S, Sakai Y, Nakamura T et al. 2017. Evolutionarily distinctive transcriptional and signaling programs drive human germ cell lineage specification from pluripotent stem cells. Cell Stem Cell 21:517–32.e5
    [Google Scholar]
  108. 108.
    Kojima-Kita K, Kuramochi-Miyagawa S, Nagamori I, Ogonuki N, Ogura A et al. 2016. MIWI2 as an effector of DNA methylation and gene silencing in embryonic male germ cells. Cell Rep. 16:2819–28
    [Google Scholar]
  109. 109.
    Kondo S, Vedanayagam J, Mohammed J, Eizadshenass S, Kan L et al. 2017. New genes often acquire male-specific functions but rarely become essential in Drosophila. Genes Dev. 31:1841–46
    [Google Scholar]
  110. 110.
    Kubota H, Avarbock MR, Brinster RL. 2004. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. PNAS 101:16489–94
    [Google Scholar]
  111. 111.
    Kubota H, Brinster RL. 2008. Culture of rodent spermatogonial stem cells, male germline stem cells of the postnatal animal. Methods Cell Biol. 86:59–84
    [Google Scholar]
  112. 112.
    Kurimoto K, Yabuta Y, Ohinata Y, Shigeta M, Yamanaka K, Saitou M. 2008. Complex genome-wide transcription dynamics orchestrated by Blimp1 for the specification of the germ cell lineage in mice. Genes Dev. 22:1617–35
    [Google Scholar]
  113. 113.
    La Manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H et al. 2018. RNA velocity of single cells. Nature 560:494–98
    [Google Scholar]
  114. 114.
    Laiho A, Kotaja N, Gyenesei A, Sironen A. 2013. Transcriptome profiling of the murine testis during the first wave of spermatogenesis. PLOS ONE 8:e61558
    [Google Scholar]
  115. 115.
    Larose H, Kent T, Ma Q, Shami AN, Harerimana N et al. 2020. Regulation of meiotic progression by Sertoli-cell androgen signaling. Mol. Biol. Cell 31:2841–62
    [Google Scholar]
  116. 116.
    Lau X, Munusamy P, Ng MJ, Sangrithi M. 2020. Single-cell RNA sequencing of the Cynomolgus macaque testis reveals conserved transcriptional profiles during mammalian spermatogenesis. Dev. Cell 54:548–66.e7
    [Google Scholar]
  117. 117.
    Law NC, Oatley MJ, Oatley JM. 2019. Developmental kinetics and transcriptome dynamics of stem cell specification in the spermatogenic lineage. Nat. Commun. 10:2787
    [Google Scholar]
  118. 118.
    Lesch BJ, Dokshin GA, Young RA, McCarrey JR, Page DC. 2013. A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis. PNAS 110:16061–66
    [Google Scholar]
  119. 119.
    Lesch BJ, Silber SJ, McCarrey JR, Page DC. 2016. Parallel evolution of male germline epigenetic poising and somatic development in animals. Nat. Genet. 48:888–94
    [Google Scholar]
  120. 120.
    Lewis SM, Asselin-Labat ML, Nguyen Q, Berthelet J, Tan X et al. 2021. Spatial omics and multiplexed imaging to explore cancer biology. Nat. Methods 18:997–1012
    [Google Scholar]
  121. 121.
    Li L, Dong J, Yan L, Yong J, Liu X et al. 2017. Single-cell RNA-seq analysis maps development of human germline cells and gonadal niche interactions. Cell Stem Cell 20:858–73.e4
    [Google Scholar]
  122. 122.
    Li M, Huang T, Li MJ, Zhang CX, Yu XC et al. 2019. The histone modification reader ZCWPW1 is required for meiosis prophase I in male but not in female mice. Sci. Adv. 5:eaax1101
    [Google Scholar]
  123. 123.
    Liao J, Ng SH, Luk AC, Suen HC, Qian Y et al. 2019. Revealing cellular and molecular transitions in neonatal germ cell differentiation using single cell RNA sequencing. Development 146:dev174953
    [Google Scholar]
  124. 124.
    Lin YN, Matzuk MM. 2014. Genetics of male fertility. Methods Mol. Biol. 1154:25–37
    [Google Scholar]
  125. 125.
    Liu H, Zhang J. 2020. Higher germline mutagenesis of genes with stronger testis expressions refutes the transcriptional scanning hypothesis. Mol. Biol. Evol. 37:3225–31
    [Google Scholar]
  126. 126.
    Long M, VanKuren NW, Chen S, Vibranovski MD 2013. New gene evolution: little did we know. Annu. Rev. Genet. 47:307–33
    [Google Scholar]
  127. 127.
    Longo SK, Guo MG, Ji AL, Khavari PA 2021. Integrating single-cell and spatial transcriptomics to elucidate intercellular tissue dynamics. Nat. Rev. Genet. 22:627–44
    [Google Scholar]
  128. 128.
    Luense LJ, Donahue G, Lin-Shiao E, Rangel R, Weller AH et al. 2019. Gcn5-mediated histone acetylation governs nucleosome dynamics in spermiogenesis. Dev. Cell 51:745–58.e6
    [Google Scholar]
  129. 129.
    Luetjens CM, Weinbauer GF, Wistuba J. 2005. Primate spermatogenesis: new insights into comparative testicular organisation, spermatogenic efficiency and endocrine control. Biol. Rev. Camb. Philos. Soc. 80:475–88
    [Google Scholar]
  130. 130.
    Luis Villanueva-Cañas J, Ruiz-Orera J, Agea MI, Gallo M, Andreu D, Albà MM 2017. New genes and functional innovation in mammals. Genome Biol. Evol. 9:1886–900
    [Google Scholar]
  131. 131.
    Lukassen S, Bosch E, Ekici AB, Winterpacht A. 2018. Characterization of germ cell differentiation in the male mouse through single-cell RNA sequencing. Sci. Rep. 8:6521
    [Google Scholar]
  132. 132.
    Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K et al. 2015. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161:1202–14
    [Google Scholar]
  133. 133.
    Maher GJ, McGowan SJ, Giannoulatou E, Verrill C, Goriely A, Wilkie AOM. 2016. Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes. PNAS 113:2454–59
    [Google Scholar]
  134. 134.
    Mahgoub M, Paiano J, Bruno M, Wu W, Pathuri S et al. 2020. Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice. eLife 9:e53360
    [Google Scholar]
  135. 135.
    Maresz K, Ponomarev ED, Barteneva N, Tan Y, Mann MK, Dittel BN. 2008. IL-13 induces the expression of the alternative activation marker Ym1 in a subset of testicular macrophages. J. Reprod. Immunol. 78:140–48
    [Google Scholar]
  136. 136.
    Matzuk MM, Lamb DJ. 2002. Genetic dissection of mammalian fertility pathways. Nat. Med. 8:S40
    [Google Scholar]
  137. 137.
    McCarrey JR. 2013. Toward a more precise and informative nomenclature describing fetal and neonatal male germ cells in rodents. Biol. Reprod. 89:47
    [Google Scholar]
  138. 138.
    McClelland KS, Bell K, Larney C, Harley VR, Sinclair AH et al. 2015. Purification and transcriptomic analysis of mouse fetal Leydig cells reveals candidate genes for specification of gonadal steroidogenic cells. Biol. Reprod. 92:145
    [Google Scholar]
  139. 139.
    Mele M, Ferreira PG, Reverter F, DeLuca DS, Monlong J et al. 2015. The human transcriptome across tissues and individuals. Science 348:660–65
    [Google Scholar]
  140. 140.
    Miyata H, Castaneda JM, Fujihara Y, Yu Z, Archambeault DR et al. 2016. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice. PNAS 113:7704–10
    [Google Scholar]
  141. 141.
    Moore L, Cagan A, Coorens THH, Neville MDC, Sanghvi R et al. 2021. The mutational landscape of human somatic and germline cells. Nature 597:381–86
    [Google Scholar]
  142. 142.
    Moretti C, Vaiman D, Tores F, Cocquet J. 2016. Expression and epigenomic landscape of the sex chromosomes in mouse post-meiotic male germ cells. Epigenet. Chromatin 9:47
    [Google Scholar]
  143. 143.
    Murat F, Mbengue N, Winge SB, Trefzer T, Leushkin E et al. 2021. The molecular evolution of spermatogenesis across mammals. bioRxiv 2021.11.08.467712. https://doi.org/10.1101/2021.11.08.467712
    [Crossref]
  144. 144.
    Nagano M, McCarrey JR, Brinster RL. 2001. Primate spermatogonial stem cells colonize mouse testes. Biol. Reprod. 64:1409–16
    [Google Scholar]
  145. 145.
    Nakaki F, Hayashi K, Ohta H, Kurimoto K, Yabuta Y, Saitou M. 2013. Induction of mouse germ-cell fate by transcription factors in vitro. Nature 501:222–26
    [Google Scholar]
  146. 146.
    Nie X, Munyoki SK, Sukhwani M, Schmid N, Missel A et al. 2022. Single-cell analysis of human testis aging and correlation with elevated body mass index. Dev. Cell 57:91160–76.e5
    [Google Scholar]
  147. 147.
    Oakberg EF. 1956. A description of spermiogenesis in the mouse and its use in analysis of the cycle of the seminiferous epithelium and germ cell renewal. Am. J. Anat. 99:391–413
    [Google Scholar]
  148. 148.
    Oakberg EF. 1971. Spermatogonial stem-cell renewal in the mouse. Anat. Rec. 169:515–31
    [Google Scholar]
  149. 149.
    Oatley JM, Avarbock MR, Telaranta AI, Fearon DT, Brinster RL. 2006. Identifying genes important for spermatogonial stem cell self-renewal and survival. PNAS 103:9524–29
    [Google Scholar]
  150. 150.
    Ohinata Y, Payer B, O'Carroll D, Ancelin K, Ono Y et al. 2005. Blimp1 is a critical determinant of the germ cell lineage in mice. Nature 436:207–13
    [Google Scholar]
  151. 151.
    O'Shaughnessy PJ, Hu L, Baker PJ. 2008. Effect of germ cell depletion on levels of specific mRNA transcripts in mouse Sertoli cells and Leydig cells. Reproduction 135:839–50
    [Google Scholar]
  152. 152.
    Palmer NO, Bakos HW, Fullston T, Lane M. 2012. Impact of obesity on male fertility, sperm function and molecular composition. Spermatogenesis 2:253–63
    [Google Scholar]
  153. 153.
    Panda SK, Colonna M. 2019. Innate lymphoid cells in mucosal immunity. Front. Immunol. 10:861
    [Google Scholar]
  154. 154.
    Park C, Qian W, Zhang J. 2012. Genomic evidence for elevated mutation rates in highly expressed genes. EMBO Rep. 13:1123–29
    [Google Scholar]
  155. 155.
    Parvinen M, Pelto-Huikko M, Söder O, Schultz R, Kaipia A et al. 1992. Expression of beta-nerve growth factor and its receptor in rat seminiferous epithelium: specific function at the onset of meiosis. J. Cell Biol. 117:629–41
    [Google Scholar]
  156. 156.
    Pezic D, Manakov SA, Sachidanandam R, Aravin AA. 2014. piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells. Genes Dev. 28:1410–28
    [Google Scholar]
  157. 157.
    Phillips BT, Gassei K, Orwig KE. 2010. Spermatogonial stem cell regulation and spermatogenesis. Philos. Trans. R. Soc. B 365:1663–78
    [Google Scholar]
  158. 158.
    Picelli S, Bjorklund AK, Faridani OR, Sagasser S, Winberg G, Sandberg R. 2013. Smart-seq2 for sensitive full-length transcriptome profiling in single cells. Nat. Methods 10:1096–98
    [Google Scholar]
  159. 159.
    Plug AW, Peters AHFM, Xu Y, Keegan KS, Hoekstra MF et al. 1997. ATM and RPA in meiotic chromosome synapsis and recombination. Nat. Genet. 17:457–61
    [Google Scholar]
  160. 160.
    Punjani N, Kang C, Lamb DJ, Schlegel PN. 2021. Current updates and future perspectives in the evaluation of azoospermia: a systematic review. Arab. J. Urol. 19:206–14
    [Google Scholar]
  161. 161.
    Raj A, van den Bogaard P, Rifkin SA, van Oudenaarden A, Tyagi S. 2008. Imaging individual mRNA molecules using multiple singly labeled probes. Nat. Methods 5:877–79
    [Google Scholar]
  162. 162.
    Ramm SA, Scharer L, Ehmcke J, Wistuba J. 2014. Sperm competition and the evolution of spermatogenesis. Mol. Hum. Reprod. 20:1169–79
    [Google Scholar]
  163. 163.
    Ramskold D, Wang ET, Burge CB, Sandberg R. 2009. An abundance of ubiquitously expressed genes revealed by tissue transcriptome sequence data. PLOS Comput. Biol. 5:e1000598
    [Google Scholar]
  164. 164.
    Rao A, Barkley D, Franca GS, Yanai I. 2021. Exploring tissue architecture using spatial transcriptomics. Nature 596:211–20
    [Google Scholar]
  165. 165.
    Rebourcet D, O'Shaughnessy PJ, Monteiro A, Milne L, Cruickshanks L et al. 2014. Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis. PLOS ONE 9:e105687
    [Google Scholar]
  166. 166.
    Rodriques SG, Stickels RR, Goeva A, Martin CA, Murray E et al. 2019. Slide-seq: a scalable technology for measuring genome-wide expression at high spatial resolution. Science 363:64341463–67
    [Google Scholar]
  167. 167.
    Romrell LJ, Bellve AR, Fawcett DW. 1976. Separation of mouse spermatogenic cells by sedimentation velocity. A morphological characterization. Dev. Biol. 49:119–31
    [Google Scholar]
  168. 168.
    Roosen-Runge EC. 1977. The Process of Spermatogenesis in Animals Cambridge, UK: Cambridge Univ. Press
  169. 169.
    Ruiz-Orera J, Hernandez-Rodriguez J, Chiva C, Sabidó E, Kondova I et al. 2015. Origins of de novo genes in human and chimpanzee. PLOS Genet 11:e1005721
    [Google Scholar]
  170. 170.
    Saitou M, Miyauchi H. 2016. Gametogenesis from pluripotent stem cells. Cell Stem Cell 18:721–35
    [Google Scholar]
  171. 171.
    Saitou M, Payer B, Lange UC, Erhardt S, Barton SC, Surani MA. 2003. Specification of germ cell fate in mice. Philos. Trans. R. Soc. B 358:1363–70
    [Google Scholar]
  172. 172.
    Sanz E, Evanoff R, Quintana A, Evans E, Miller JA et al. 2013. RiboTag analysis of actively translated mRNAs in Sertoli and Leydig cells in vivo. PLOS ONE 8:e66179
    [Google Scholar]
  173. 173.
    Sasagawa Y, Nikaido I, Hayashi T, Danno H, Uno KD et al. 2013. Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity. Genome Biol 14:3097
    [Google Scholar]
  174. 174.
    Sasaki K, Nakamura T, Okamoto I, Yabuta Y, Iwatani C et al. 2016. The germ cell fate of cynomolgus monkeys is specified in the nascent amnion. Dev. Cell 39:169–85
    [Google Scholar]
  175. 175.
    Schafer M, Nayernia K, Engel W, Schafer U. 1995. Translational control in spermatogenesis. Dev. Biol. 172:344–52
    [Google Scholar]
  176. 176.
    Schmidt EE. 1996. Transcriptional promiscuity in testes. Curr. Biol. 6:768–69
    [Google Scholar]
  177. 177.
    Schultz N, Hamra FK, Garbers DL. 2003. A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets. PNAS 100:12201–6
    [Google Scholar]
  178. 178.
    Sczyrba A, Hofmann P, Belmann P, Koslicki D, Janssen S et al. 2017. Critical assessment of metagenome interpretation—a benchmark of metagenomics software. Nat. Methods 14:1063–71
    [Google Scholar]
  179. 179.
    Selby CP, Sancar A. 1993. Molecular mechanism of transcription-repair coupling. Science 260:53–58
    [Google Scholar]
  180. 180.
    Shah S, Takei Y, Zhou W, Lubeck E, Yun J et al. 2018. Dynamics and spatial genomics of the nascent transcriptome by Intron seqFISH. Cell 174:363–76.e16
    [Google Scholar]
  181. 181.
    Shalek AK, Satija R, Adiconis X, Gertner RS, Gaublomme JT et al. 2013. Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells. Nature 498:236–40
    [Google Scholar]
  182. 182.
    Shami AN, Zheng X, Munyoki SK, Ma Q, Manske GL et al. 2020. Single-cell RNA sequencing of human, macaque, and mouse testes uncovers conserved and divergent features of mammalian spermatogenesis. Dev. Cell 54:529–47.e12
    [Google Scholar]
  183. 183.
    Shapiro E, Biezuner T, Linnarsson S. 2013. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat. Rev. Genet. 14:618–30
    [Google Scholar]
  184. 184.
    Shen Y-C, Shami AN, Moritz L, Larose H, Manske GL et al. 2021. TCF21+ mesenchymal cells contribute to testis somatic cell development, homeostasis, and regeneration in mice. Nat. Commun. 12:3876
    [Google Scholar]
  185. 185.
    Sleutels F, Soochit W, Bartkuhn M, Heath H, Dienstbach S et al. 2012. The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner. Epigenet. Chromatin 5:8
    [Google Scholar]
  186. 186.
    Soderström K-O, Parvinen M. 1976. RNA synthesis in different stages of rat seminiferous epithelial cycle. Mol. Cell. Endocrinol. 5:181–99
    [Google Scholar]
  187. 187.
    Sohni A, Tan K, Song H-W, Burow D, de Rooij DG et al. 2019. The neonatal and adult human testis defined at the single-cell level. Cell Rep 26:1501–17.e4
    [Google Scholar]
  188. 188.
    Soumillon M, Necsulea A, Weier M, Brawand D, Zhang X et al. 2013. Cellular source and mechanisms of high transcriptome complexity in the mammalian testis. Cell Rep. 3:2179–90
    [Google Scholar]
  189. 189.
    Stickels RR, Murray E, Kumar P, Li J, Marshall JL et al. 2021. Highly sensitive spatial transcriptomics at near-cellular resolution with Slide-seqV2. Nat. Biotechnol. 39:313–19
    [Google Scholar]
  190. 190.
    Sun X, Brieño-Enríquez MA, Cornelius A, Modzelewski AJ, Maley TT et al. 2016. FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion during embryogenesis and altered processing of crossover sites during meiotic prophase I in mice. Chromosoma 125:237–52
    [Google Scholar]
  191. 191.
    Surani MA. 2004. Stem cells: how to make eggs and sperm. Nature 427:106–7
    [Google Scholar]
  192. 192.
    Suzuki H, Ahn HW, Chu T, Bowden W, Gassei K et al. 2012. SOHLH1 and SOHLH2 coordinate spermatogonial differentiation. Dev. Biol. 361:301–12
    [Google Scholar]
  193. 193.
    Suzuki S, McCarrey JR, Hermann BP. 2021. An mTORC1-dependent switch orchestrates the transition between mouse spermatogonial stem cells and clones of progenitor spermatogonia. Cell Rep. 34:108752
    [Google Scholar]
  194. 194.
    Syed V, Hecht NB. 2001. Selective loss of Sertoli cell and germ cell function leads to a disruption in Sertoli cell-germ cell communication during aging in the brown Norway Rat. Biol. Reprod. 64:107–12
    [Google Scholar]
  195. 195.
    Tan K, Song H-W, Thompson M, Munyoki S, Sukhwani M et al. 2020. Transcriptome profiling reveals signaling conditions dictating human spermatogonia fate in vitro. PNAS 117:17832–41
    [Google Scholar]
  196. 196.
    Tan K, Song H-W, Wilkinson MF. 2020. Single-cell RNAseq analysis of testicular germ and somatic cell development during the perinatal period. Development 147:dev183251
    [Google Scholar]
  197. 197.
    Testa E, Nardozi D, Antinozzi C, Faieta M, Di Cecca S et al. 2018. H2AFX and MDC1 promote maintenance of genomic integrity in male germ cells. J. Cell Sci. 131:6jcs214411
    [Google Scholar]
  198. 198.
    Tourtellotte WG, Nagarajan R, Bartke A, Milbrandt J. 2000. Functional compensation by Egr4 in Egr1-dependent luteinizing hormone regulation and Leydig cell steroidogenesis. Mol. Cell. Biol. 20:5261–68
    [Google Scholar]
  199. 199.
    Tsai MY, Yeh SD, Wang RS, Yeh S, Zhang C et al. 2006. Differential effects of spermatogenesis and fertility in mice lacking androgen receptor in individual testis cells. PNAS 103:18975–80
    [Google Scholar]
  200. 200.
    Turner JM. 2007. Meiotic sex chromosome inactivation. Development 134:1823–31
    [Google Scholar]
  201. 201.
    Valli H, Phillips BT, Orwig KE, Gassei K, Nagano MC. 2015. Spermatogonial stem cells and spermatogenesis. Knobil Neill's Physiol. Reprod. 1:595–635
    [Google Scholar]
  202. 202.
    Valli H, Sukhwani M, Dovey SL, Peters KA, Donohue J et al. 2014. Fluorescence- and magnetic-activated cell sorting strategies to isolate and enrich human spermatogonial stem cells. Fertil. Steril. 102:566–80.e7
    [Google Scholar]
  203. 203.
    Vasiliauskaite L, Vitsios D, Berrens RV, Carrieri C, Reik W et al. 2017. A MILI-independent piRNA biogenesis pathway empowers partial germline reprogramming. Nat. Struct. Mol. Biol. 24:604–6
    [Google Scholar]
  204. 204.
    Vitti JJ, Grossman SR, Sabeti PC. 2013. Detecting natural selection in genomic data. Annu. Rev. Genet. 47:97–120
    [Google Scholar]
  205. 205.
    Wang J, Tang C, Wang Q, Su J, Ni T et al. 2017. NRF1 coordinates with DNA methylation to regulate spermatogenesis. FASEB J. 31:4959–70
    [Google Scholar]
  206. 206.
    Wang M, Liu X, Chang G, Chen Y, An G et al. 2018. Single-cell RNA sequencing analysis reveals sequential cell fate transition during human spermatogenesis. Cell Stem Cell 23:599–614.e4
    [Google Scholar]
  207. 207.
    Wang Z-Y, Leushkin E, Liechti A, Ovchinnikova S, Mößinger K et al. 2020. Transcriptome and translatome co-evolution in mammals. Nature 588:642–47
    [Google Scholar]
  208. 208.
    White-Cooper H, Bausek N. 2010. Evolution and spermatogenesis. Philos. Trans. R. Soc. B 365:1465–80
    [Google Scholar]
  209. 209.
    Wilbrey-Clark A, Roberts K, Teichmann SA. 2020. Cell Atlas technologies and insights into tissue architecture. Biochem. J. 477:81427–42
    [Google Scholar]
  210. 210.
    Wistuba J, Schrod A, Greve B, Hodges JK, Aslam H et al. 2003. Organization of seminiferous epithelium in primates: relationship to spermatogenic efficiency, phylogeny, and mating system. Biol. Reprod. 69:582–91
    [Google Scholar]
  211. 211.
    Wright WW, Smith L, Kerr C, Charron M. 2003. Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis. Biol. Reprod. 68:680–87
    [Google Scholar]
  212. 212.
    Wu AR, Neff NF, Kalisky T, Dalerba P, Treutlein B et al. 2014. Quantitative assessment of single-cell RNA-sequencing methods. Nat. Methods 11:41–46
    [Google Scholar]
  213. 213.
    Xia B, Yan Y, Baron M, Wagner F, Barkley D et al. 2020. Widespread transcriptional scanning in the testis modulates gene evolution rates. Cell 180:248–62.e21
    [Google Scholar]
  214. 214.
    Xia C, Fan J, Emanuel G, Hao J, Zhuang X. 2019. Spatial transcriptome profiling by MERFISH reveals subcellular RNA compartmentalization and cell cycle-dependent gene expression. PNAS 116:19490–99
    [Google Scholar]
  215. 215.
    Xue Z, Huang K, Cai C, Cai L, Jiang CY et al. 2013. Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature 500:593–97
    [Google Scholar]
  216. 216.
    Yamanaka S, Nishihara H, Toh H, Eijy Nagai LA, Hashimoto K et al. 2019. Broad heterochromatic domains open in gonocyte development prior to de novo DNA methylation. Dev. Cell 51:21–34.e5
    [Google Scholar]
  217. 217.
    Yamashiro C, Sasaki K, Yabuta Y, Kojima Y, Nakamura T et al. 2018. Generation of human oogonia from induced pluripotent stem cells in vitro. Science 362:356–60
    [Google Scholar]
  218. 218.
    Yapar E, Saglican E, Dönertaş HM, Özkurt E, Yan Z et al. 2021. Convergent evolution of primate testis transcriptomes reflects mating strategy. bioRxiv 010553. https://doi.org/10.1101/010553
    [Crossref]
  219. 219.
    Yatsenko AN, Iwamori N, Iwamori T, Matzuk MM. 2010. The power of mouse genetics to study spermatogenesis. J. Androl. 31:34–44
    [Google Scholar]
  220. 220.
    Yoshida S, Sukeno M, Nabeshima Y. 2007. A vasculature-associated niche for undifferentiated spermatogonia in the mouse testis. Science 317:1722–26
    [Google Scholar]
  221. 221.
    Yoshida S, Sukeno M, Nakagawa T, Ohbo K, Nagamatsu G et al. 2006. The first round of mouse spermatogenesis is a distinctive program that lacks the self-renewing spermatogonia stage. Development 133:1495–505
    [Google Scholar]
  222. 222.
    Yoshida S, Takakura A, Ohbo K, Abe K, Wakabayashi J et al. 2004. Neurogenin3 delineates the earliest stages of spermatogenesis in the mouse testis. Dev. Biol. 269:447–58
    [Google Scholar]
  223. 223.
    Zhang J-Y, Zhou Q. 2019. On the regulatory evolution of new genes throughout their life history. Mol. Biol. Evol. 36:15–27
    [Google Scholar]
  224. 224.
    Zhao L, Saelao P, Jones CD, Begun DJ. 2014. Origin and spread of de novo genes in Drosophila melanogaster populations. Science 343:769–72
    [Google Scholar]
  225. 225.
    Zhao LY, Yao CC, Xing XY, Jing T, Li P et al. 2020. Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells. Nat. Commun. 11:5683
    [Google Scholar]
  226. 226.
    Zhu C, Preissl S, Ren B. 2020. Single-cell multimodal omics: the power of many. Nat. Methods 17:11–14
    [Google Scholar]
  227. 227.
    Zimmermann C, Stevant I, Borel C, Conne B, Pitetti JL et al. 2015. Research resource: the dynamic transcriptional profile of Sertoli cells during the progression of spermatogenesis. Mol. Endocrinol. 29:627–42
    [Google Scholar]
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