Journal Article

DKFZ-2024-00315

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The dynamic genetic determinants of increased transcriptional divergence in spermatids.

Panten, J. (First author)DKFZ* ; Heinen, T.DKFZ* ; Ernst, C. ; Eling, N. ; Wagner, R. E.DKFZ* ; Satorius, M.DKFZ* ; Marioni, J. C. ; Stegle, O.DKFZ* ; Odom, D. (Last author)DKFZ*

2024
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-024-45133-1

Abstract: 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.

Note: #EA:B260#EA:B270#LA:B260#LA:B270#

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Contributing Institute(s):

1. B270 Regulatorische Genomik und Evolution von Tumoren (B270)
2. B260 Bioinformatik der Genomik und Systemgenetik (B260)
3. A350 Reguläre Mechanismen der Genexpression (A350)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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