Abstract
BackgroundAs sex determines mammalian development, understanding the nature and developmental dynamics of the sexually dimorphic transcriptome is important. To explore this, we generated 76 genome-wide RNA-seq profiles from mouse eight-cell embryos, late gestation and adult livers, together with 4 ground-state pluripotent embryonic (ES) cell lines from which we generated both RNA-seq and multiple ChIP-seq profiles. We complemented this with previously published data to yield 5 snap-shots of pre-implantation development, late-gestation placenta and somatic tissue and multiple adult tissues for integrative analysis.ResultsWe define a high-confidence sex-dimorphic signature of 69 genes in eight-cell embryos. Sex-chromosome-linked components of this signature are largely conserved throughout pre-implantation development and in ES cells, whilst the autosomal component is more dynamic. Sex-biased gene expression is reflected by enrichment for activating and repressive histone modifications. The eight-cell signature is largely non-overlapping with that defined from fetal liver, neither was it correlated with adult liver or other tissues analysed. The number of sex-dimorphic genes increases throughout development. We identified many more dimorphic genes in adult compared to fetal liver. However, approximately two thirds of the dimorphic genes identified in fetal liver were also dimorphic in adult liver. Sex-biased expression differences unique to adult liver were enriched for growth hormone-responsiveness. Sexually dimorphic gene expression in pre-implantation development is driven by sex-chromosome based transcription, whilst later development is characterised by sex dimorphic autosomal transcription.ConclusionThis systematic study identifies three distinct phases of sex dimorphism throughout mouse development, and has significant implications for understanding the developmental origins of sex-specific phenotypes and disease in mammals.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1506-4) contains supplementary material, which is available to authorized users.
Highlights
As sex determines mammalian development, understanding the nature and developmental dynamics of the sexually dimorphic transcriptome is important
Dimorphic gene expression emerges very early in development Eight-cell embryos provide the first snap-shot in mice after the initiation of embryonic genome activation at the 2 cell stage, when maternal transcripts have been depleted [13,14]
We detected 13 469 transcripts expressed across all eight cell embryos, which is greater than previous microarrays of blastocysts, but less than other RNA-seq data from eight cell embryos that was sequenced at greater depth [11,14]
Summary
As sex determines mammalian development, understanding the nature and developmental dynamics of the sexually dimorphic transcriptome is important. We generated 76 genome-wide RNA-seq profiles from mouse eight-cell embryos, late gestation and adult livers, together with 4 ground-state pluripotent embryonic (ES) cell lines from which we generated both RNA-seq and multiple ChIP-seq profiles. We complemented this with previously published data to yield 5 snap-shots of pre-implantation development, late-gestation placenta and somatic tissue and multiple adult tissues for integrative analysis. This developmental divergence arises as a consequence of sex-chromosome complement and is largely, not exclusively mediated through the organisational and activational effects of sex-specific hormones [1]. Animal models of the Developmental Origins of Health and Disease
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