%0 Journal Article
%A Panten, Jasper
%A Heinen, Tobias
%A Ernst, Christina
%A Eling, Nils
%A Wagner, Rebecca E
%A Satorius, Maja
%A Marioni, John C
%A Stegle, Oliver
%A Odom, Duncan
%T The dynamic genetic determinants of increased transcriptional divergence in spermatids.
%J Nature Communications
%V 15
%N 1
%@ 2041-1723
%C [London]
%I Nature Publishing Group UK
%M DKFZ-2024-00315
%P 1272
%D 2024
%Z #EA:B260#EA:B270#LA:B260#LA:B270#
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38341412
%2 pmc:PMC10858866
%R 10.1038/s41467-024-45133-1
%U https://inrepo02.dkfz.de/record/288057