Panten, JasperHeinen, TobiasErnst, ChristinaEling, NilsWagner, Rebecca E.Satorius, MajaMarioni, John C.Stegle, OliverOdom, Duncan T.2024-03-182024-03-182024-03-182024-02-1010.1038/s41467-024-45133-1https://infoscience.epfl.ch/handle/20.500.14299/206370WOS:001160036000021Cis-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.|Here the authors show that genetic changes between species often alter gene expression in a cell type-specific manner. Most of this variability is driven by locally functioning cis-acting variation, and this contributes to the speed at which cell types accumulate expression changes.Evolutionary ChangesExpressionCisMacaquetext::journal::journal article::research article