The dynamic genetic determinants of increased transcriptional divergence in spermatids

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 spermatogeni...

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Hauptverfasser: Panten, Jasper (VerfasserIn) , Heinen, Tobias (VerfasserIn) , Ernst, Christina (VerfasserIn) , Eling, Nils (VerfasserIn) , Wagner, Rebecca E. (VerfasserIn) , Satorius, Maja (VerfasserIn) , Marioni, John C. (VerfasserIn) , Stegle, Oliver (VerfasserIn) , Odom, Duncan T. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 10 February 2024
In: Nature Communications
Year: 2024, Jahrgang: 15, Pages: 1-13
ISSN:2041-1723
DOI:10.1038/s41467-024-45133-1
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-024-45133-1
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Verfasserangaben:Jasper Panten, Tobias Heinen, Christina Ernst, Nils Eling, Rebecca E. Wagner, Maja Satorius, John C. Marioni, Oliver Stegle & Duncan T. Odom

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520 |a 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. 
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