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Dynamics of Meiotic Sex Chromosome Inactivation and Pachytene Activation in Mice Spermatogenesis

View ORCID ProfileÁbel Vértesy, Javier Frias-Aldeguer, Zeliha Sahin, Nicolas Rivron, Alexander van Oudenaarden, Niels Geijsen
doi: https://doi.org/10.1101/665372
Ábel Vértesy
1Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center, 3584 CT Utrecht, The Netherlands
2Department of Genetics, Center for Molecular Medicine, Cancer Genomics Netherlands, University Medical Center Utrecht, The Netherlands
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  • ORCID record for Ábel Vértesy
  • For correspondence: abel.vertesy@gmail.com
Javier Frias-Aldeguer
1Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center, 3584 CT Utrecht, The Netherlands
4MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, The Netherlands
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Zeliha Sahin
1Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center, 3584 CT Utrecht, The Netherlands
3Academic Medical Center, Amsterdam, The Netherlands
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Nicolas Rivron
1Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center, 3584 CT Utrecht, The Netherlands
4MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, The Netherlands
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Alexander van Oudenaarden
1Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center, 3584 CT Utrecht, The Netherlands
2Department of Genetics, Center for Molecular Medicine, Cancer Genomics Netherlands, University Medical Center Utrecht, The Netherlands
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Niels Geijsen
1Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center, 3584 CT Utrecht, The Netherlands
5Faculty of Veterinary Medicine, Clinical Sciences of Companion Animals, Utrecht University, The Netherlands
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Abstract

During germ cell development, cells undergo a drastic switch from mitosis to meiosis to form haploid germ cells. Sequencing and computational technologies now allow studying development at the single-cell level. Here we developed a multiplexed trajectory reconstruction to create a high-resolution developmental map of spermatogonia and prophase-I spermatocytes from testes of a Dazl-GFP reporter mouse. We identified three main transitions in the meiotic prophase-I: meiotic entry, the meiotic sex chromosome inactivation (MSCI), and concomitant pachytene activation. We validated the key features of these transitions in vivo using single molecule FISH. Focusing on MSCI, we found that 34% of sex chromosomal genes are induced shortly before MSCI, that silencing time is diverse and correlates with specific gene functions. These highlight a previously underappreciated level of regulation of MSCI. Finally, we found that spermatozoal genes in pachytene are activated in a temporal pattern reflecting the future anatomic and functional order of the sperm cell. Altogether we highlighted how precise and sequential changes in gene expression regulate cellular states in meiotic prophase-I.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted June 10, 2019.
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Dynamics of Meiotic Sex Chromosome Inactivation and Pachytene Activation in Mice Spermatogenesis
Ábel Vértesy, Javier Frias-Aldeguer, Zeliha Sahin, Nicolas Rivron, Alexander van Oudenaarden, Niels Geijsen
bioRxiv 665372; doi: https://doi.org/10.1101/665372
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Dynamics of Meiotic Sex Chromosome Inactivation and Pachytene Activation in Mice Spermatogenesis
Ábel Vértesy, Javier Frias-Aldeguer, Zeliha Sahin, Nicolas Rivron, Alexander van Oudenaarden, Niels Geijsen
bioRxiv 665372; doi: https://doi.org/10.1101/665372

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