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The dynamic genetic determinants of increased transcriptional divergence in spermatids

Author

Listed:
  • Jasper Panten

    (German Cancer Research Centre (DKFZ)
    German Cancer Research Centre (DKFZ)
    Heidelberg University)

  • Tobias Heinen

    (German Cancer Research Centre (DKFZ)
    Heidelberg University
    Genome Biology Unit)

  • Christina Ernst

    (Ecole Polytechnique Fédérale de Lausanne (EPFL))

  • Nils Eling

    (University of Zurich, Department of Quantitative Biomedicine
    ETH Zurich, Institute for Molecular Health Sciences)

  • Rebecca E. Wagner

    (Heidelberg University
    German Cancer Research Centre (DKFZ))

  • Maja Satorius

    (German Cancer Research Centre (DKFZ))

  • John C. Marioni

    (University of Cambridge
    Wellcome Genome Campus
    Wellcome Genome Campus)

  • Oliver Stegle

    (German Cancer Research Centre (DKFZ)
    Genome Biology Unit)

  • Duncan T. Odom

    (German Cancer Research Centre (DKFZ)
    Heidelberg University
    University of Cambridge)

Abstract

Cis-genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- and trans-effects act across continuous trajectories of cellular differentiation in vivo is poorly understood. Here, we quantify allele-specific expression during spermatogenic differentiation at single-cell resolution in an F1 hybrid mouse system, allowing for the comprehensive characterisation of cis- and trans-genetic effects, including their dynamics across cellular differentiation. Collectively, almost half of the genes subject to genetic regulation show evidence for dynamic cis-effects that vary during differentiation. Our system also allows us to robustly identify dynamic trans-effects, which are less pervasive than cis-effects. In aggregate, genetic effects were strongest in round spermatids, which parallels their increased transcriptional divergence we identified between species. Our approach provides a comprehensive quantification of the variability of genetic effects in vivo, and demonstrates a widely applicable strategy to dissect the impact of regulatory variants on gene regulation in dynamic systems.

Suggested Citation

  • Jasper Panten & Tobias Heinen & Christina Ernst & Nils Eling & Rebecca E. Wagner & Maja Satorius & John C. Marioni & Oliver Stegle & Duncan T. Odom, 2024. "The dynamic genetic determinants of increased transcriptional divergence in spermatids," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45133-1
    DOI: 10.1038/s41467-024-45133-1
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