A genomic atlas of human adrenal and gonad development

Del Valle, Ignacio, Buonocore, Federica, Duncan, Andrew J., Lin, Lin, Barenco, Martino, Parnaik, Rahul, Shah, Sonia, Hubank, Mike, Gerrelli, Dianne and Achermann, John C. (2017) A genomic atlas of human adrenal and gonad development. Wellcome Open Research, 2 1-42. doi:10.12688/wellcomeopenres.11253.2

Author Del Valle, Ignacio
Buonocore, Federica
Duncan, Andrew J.
Lin, Lin
Barenco, Martino
Parnaik, Rahul
Shah, Sonia
Hubank, Mike
Gerrelli, Dianne
Achermann, John C.
Title A genomic atlas of human adrenal and gonad development
Journal name Wellcome Open Research   Check publisher's open access policy
ISSN 2398-502X
Publication date 2017-04-07
Year available 2017
Sub-type Article (original research)
DOI 10.12688/wellcomeopenres.11253.2
Open Access Status DOI
Volume 2
Start page 1
End page 42
Total pages 42
Place of publication London, United Kingdom
Publisher Wellcome Trust
Abstract 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.

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.

Using this approach, we have identified novel components of adrenal development (e.g. ASB4, NPR3) and confirmed the role of SRY as the main human testis-determining gene. By mathematical modelling time-series data we have found new genes up-regulated with SOX9 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.

This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders.
Keyword adrenal
gene expression
germ cell
human development
sex development
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 098513
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
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Created: Wed, 10 Jan 2018, 16:54:30 EST