A genomic atlas of human adrenal and gonad development

Wellcome Open Research

article

Ignacio del Valle¹  Federica Buonocore¹  Andrew J. Duncan¹  Lin Lin¹  Martino Barenco²  Rahul Parnaik¹  Sonia Shah³  Mike Hubank⁵  Dianne Gerrelli²  John C. Achermann¹ 

[1] Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health;Developmental Biology and Cancer, UCL Great Ormond Street Institute of Child Health;Institute for Molecular Bioscience, University of Queensland;Institute of Cardiovascular Science, University College London;The Centre for Molecular Pathology, Royal Marsden Hospital

关键词: adrenal;    testis;    ovary;    sex development;    steroidogenesis;    germ cell;    human development;    gene expression;   

DOI  :  10.12688/wellcomeopenres.11253.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: In humans, the adrenal glands and gonads undergo distinct biological events between 6-10 weeks post conception (wpc), such as testis determination, the onset of steroidogenesis and primordial germ cell development. However, relatively little is currently known about the genetic mechanisms underlying these processes. We therefore aimed to generate a detailed genomic atlas of adrenal and gonad development across these critical stages of human embryonic and fetal development.Methods: RNA was extracted from 53 tissue samples between 6-10 wpc (adrenal, testis, ovary and control). Affymetrix array analysis was performed and differential gene expression was analysed using Bioconductor. A mathematical model was constructed to investigate time-series changes across the dataset. Pathway analysis was performed using ClueGo and cellular localisation of novel factors confirmed using immunohistochemistry.Results: Using this approach, we have identified novel components of adrenal development (e.g.ASB4,NPR3) and confirmed the role ofSRY as the main human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated withSOX9 in the testis (e.g.CITED1), which may represent components of the testis development pathway. We have shown that testicular steroidogenesis has a distinct onset at around 8 wpc and identified potential novel components in adrenal and testicular steroidogenesis (e.g.MGARP,FOXO4,MAP3K15,GRAMD1B,RMND2), as well as testis biomarkers (e.g.SCUBE1). We have also shown that the developing human ovary expresses distinct subsets of genes (e.g. OR10G9,OR4D5), but enrichment for established biological pathways is limited.Conclusion: This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders.

【 授权许可】

CC BY