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000288057 245__ $$aThe dynamic genetic determinants of increased transcriptional divergence in spermatids.
000288057 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000288057 520__ $$aCis-genetic effects are key determinants of transcriptional divergence in discrete tissues and cell types. However, how cis- and trans-effects act across continuous trajectories of cellular differentiation in vivo is poorly understood. Here, we quantify allele-specific expression during spermatogenic differentiation at single-cell resolution in an F1 hybrid mouse system, allowing for the comprehensive characterisation of cis- and trans-genetic effects, including their dynamics across cellular differentiation. Collectively, almost half of the genes subject to genetic regulation show evidence for dynamic cis-effects that vary during differentiation. Our system also allows us to robustly identify dynamic trans-effects, which are less pervasive than cis-effects. In aggregate, genetic effects were strongest in round spermatids, which parallels their increased transcriptional divergence we identified between species. Our approach provides a comprehensive quantification of the variability of genetic effects in vivo, and demonstrates a widely applicable strategy to dissect the impact of regulatory variants on gene regulation in dynamic systems.
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000288057 7001_ $$0P:(DE-He78)3dca76fdaa21d3d5437373129e4db905$$aHeinen, Tobias$$b1$$udkfz
000288057 7001_ $$00000-0002-3569-2209$$aErnst, Christina$$b2
000288057 7001_ $$00000-0002-4711-1176$$aEling, Nils$$b3
000288057 7001_ $$0P:(DE-He78)3ffdda266b4958f6a267fa2ce18f2762$$aWagner, Rebecca E$$b4$$udkfz
000288057 7001_ $$0P:(DE-He78)ca008c6f8f25a3e23bc85d19418d9558$$aSatorius, Maja$$b5
000288057 7001_ $$00000-0001-9092-0852$$aMarioni, John C$$b6
000288057 7001_ $$0P:(DE-He78)9aabcfee1a1fc9202398a45a63f0b1e3$$aStegle, Oliver$$b7$$udkfz
000288057 7001_ $$0P:(DE-He78)4c21317940f3ec566480ebcdcff3e00c$$aOdom, Duncan$$b8$$eLast author$$udkfz
000288057 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-45133-1$$gVol. 15, no. 1, p. 1272$$n1$$p1272$$tNature Communications$$v15$$x2041-1723$$y2024
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