Single-nucleus resolution of sex-biased expression and dosage compensation in Drosophila melanogaster De Castro Barbosa Rodrigues Barata, Carolina ; https://orcid.org/0000-0003-1945-2245 Vicoso, Beatriz ; https://orcid.org/0000-0002-4579-8306 ddc:570 In many species, sex-biased expression is widespread and thought to contribute to sexual dimorphism. While bulk RNA-sequencing has been instrumental in identifying strongly sex-biased genes, it lacks resolution to assess variation across cell-types and tissue compartments. Using single-nucleus expression data from the Fly Cell Atlas, we investigate sex differences in adult Drosophila melanogaster. We find that differences in cell-type composition between the sexes are not a major source of sex-bias, as for the vast majority of genes, the degree of sex-bias is similar regardless of whether sex differences in cell-type composition are controlled for or not. Our analysis confirms a deficit of X-linked male-biased genes in the body’s somatic tissues that is widespread across cell-types. We also find the excess of X-linked female-biased genes to be associated with nervous system cells in the head but with epithelial cells in the body’s somatic tissues, showing that single-nucleus data crucially resolves sex-bias at the cell-type level. We investigate dosage compensation (DC) across 15 tissues and 17 cell-types. We observe that it varies throughout the body. Surprisingly, we observe a lack of DC in a cluster of main cells within the male accessory glands. This result highlights the importance of understanding context-dependent DC. Royal Society of London 2026 info:eu-repo/semantics/article doc-type:article text http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/21161 https://research-explorer.ista.ac.at/download/21161/21226 de Castro Barbosa Rodrigues Barata C, Vicoso B. Single-nucleus resolution of sex-biased expression and dosage compensation in Drosophila melanogaster. <i>Proceedings of the Royal Society B Biological Sciences</i>. 2026;293(2063). doi:<a href="https://doi.org/10.1098/rspb.2025.2471">10.1098/rspb.2025.2471</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1098/rspb.2025.2471 info:eu-repo/semantics/altIdentifier/e-issn/1471-2954 info:eu-repo/semantics/altIdentifier/pmid/41592777 info:eu-repo/semantics/openAccess