Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals

Biology of Sex Differences

Research

Victorya Richardson¹  Rob J. Kulathinal²  Nora Engel³ 

[1] Department of Biology, Temple University, 1900 N. 12th Street, 19122, Philadelphia, PA, USA;Department of Biology, Temple University, 1900 N. 12th Street, 19122, Philadelphia, PA, USA;Institute for Genomics and Evolutionary Medicine, Temple University, 19122, Philadelphia, PA, USA;Department of Cancer Biology, Lewis Katz School of Medicine, Fels Cancer Institute for Personalized Medicine, Temple University, 3400 N. Broad Street, 19140, Philadelphia, PA, USA;

关键词: Sex-biased gene expression;    Evolutionary development;    Genomics;    Mammalian embryogenesis;   

DOI  :  10.1186/s13293-023-00520-z

 received in 2022-11-16, accepted in 2023-05-15,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMammalian gonadal sex is determined by the presence or absence of a Y chromosome and the subsequent production of sex hormones contributes to secondary sexual differentiation. However, sex chromosome-linked genes encoding dosage-sensitive transcription and epigenetic factors are expressed well before gonad formation and have the potential to establish sex-biased expression that persists beyond the appearance of gonadal hormones. Here, we apply a comparative bioinformatics analysis on a pair of published single-cell datasets from mouse and human during very early embryogenesis—from two-cell to pre-implantation stages—to characterize sex-specific signals and to assess the degree of conservation among early acting sex-specific genes and pathways.ResultsClustering and regression analyses of gene expression across samples reveal that sex initially plays a significant role in overall gene expression patterns at the earliest stages of embryogenesis which potentially may be the byproduct of signals from male and female gametes during fertilization. Although these transcriptional sex effects rapidly diminish, sex-biased genes appear to form sex-specific protein–protein interaction networks across pre-implantation stages in both mammals providing evidence that sex-biased expression of epigenetic enzymes may establish sex-specific patterns that persist beyond pre-implantation. Non-negative matrix factorization (NMF) on male and female transcriptomes generated clusters of genes with similar expression patterns across sex and developmental stages, including post-fertilization, epigenetic, and pre-implantation ontologies conserved between mouse and human. While the fraction of sex-differentially expressed genes (sexDEGs) in early embryonic stages is similar and functional ontologies are conserved, the genes involved are generally different in mouse and human.ConclusionsThis comparative study uncovers much earlier than expected sex-specific signals in mouse and human embryos that pre-date hormonal signaling from the gonads. These early signals are diverged with respect to orthologs yet conserved in terms of function with important implications in the use of genetic models for sex-specific disease.

【 授权许可】

CC BY   
© The Author(s) 2023

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