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Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals
BACKGROUND: Mammalian 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 expresse...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199522/ https://www.ncbi.nlm.nih.gov/pubmed/37208698 http://dx.doi.org/10.1186/s13293-023-00520-z |
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author | Richardson, Victorya Engel, Nora Kulathinal, Rob J. |
author_facet | Richardson, Victorya Engel, Nora Kulathinal, Rob J. |
author_sort | Richardson, Victorya |
collection | PubMed |
description | BACKGROUND: Mammalian 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. RESULTS: Clustering 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. CONCLUSIONS: This 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13293-023-00520-z. |
format | Online Article Text |
id | pubmed-10199522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101995222023-05-21 Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals Richardson, Victorya Engel, Nora Kulathinal, Rob J. Biol Sex Differ Research BACKGROUND: Mammalian 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. RESULTS: Clustering 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. CONCLUSIONS: This 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13293-023-00520-z. BioMed Central 2023-05-19 /pmc/articles/PMC10199522/ /pubmed/37208698 http://dx.doi.org/10.1186/s13293-023-00520-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Richardson, Victorya Engel, Nora Kulathinal, Rob J. Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals |
title | Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals |
title_full | Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals |
title_fullStr | Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals |
title_full_unstemmed | Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals |
title_short | Comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals |
title_sort | comparative developmental genomics of sex-biased gene expression in early embryogenesis across mammals |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10199522/ https://www.ncbi.nlm.nih.gov/pubmed/37208698 http://dx.doi.org/10.1186/s13293-023-00520-z |
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