TY  - JOUR
AU  - Panten, Jasper
AU  - Heinen, Tobias
AU  - Ernst, Christina
AU  - Eling, Nils
AU  - Wagner, Rebecca E
AU  - Satorius, Maja
AU  - Marioni, John C
AU  - Stegle, Oliver
AU  - Odom, Duncan
TI  - The dynamic genetic determinants of increased transcriptional divergence in spermatids.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DKFZ-2024-00315
SP  - 1272
PY  - 2024
N1  - #EA:B260#EA:B270#LA:B260#LA:B270#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:38341412
C2  - pmc:PMC10858866
DO  - DOI:10.1038/s41467-024-45133-1
UR  - https://inrepo02.dkfz.de/record/288057
ER  -