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Publication : The dynamic genetic determinants of increased transcriptional divergence in spermatids.

First Author  Panten J Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  1272
PubMed ID  38341412 Mgi Jnum  J:357252
Mgi Id  MGI:7594921 Doi  10.1038/s41467-024-45133-1
Citation  Panten J, et al. (2024) The dynamic genetic determinants of increased transcriptional divergence in spermatids. Nat Commun 15(1):1272
abstractText  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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