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dc.contributor.authorDel Valle, Ien_US
dc.contributor.authorBuonocore, Fen_US
dc.contributor.authorDuncan, AJen_US
dc.contributor.authorLin, Len_US
dc.contributor.authorBarenco, Men_US
dc.contributor.authorParnaik, Ren_US
dc.contributor.authorShah, Sen_US
dc.contributor.authorHubank, Men_US
dc.contributor.authorGerrelli, Den_US
dc.contributor.authorAchermann, JCen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2017-12-19T15:22:42Z
dc.date.issued2017-04-07en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28459107en_US
dc.identifier.citationWellcome Open Res, 2017, 2 pp. 25 - ?en_US
dc.identifier.issn2398-502Xen_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/983
dc.identifier.doi10.12688/wellcomeopenres.11253.2en_US
dc.description.abstractBACKGROUND: 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 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. CONCLUSION: This genomic atlas is revealing important novel aspects of human development and new candidate genes for adrenal and reproductive disorders.en_US
dc.format.extent25 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectadrenalen_US
dc.subjectgene expressionen_US
dc.subjectgerm cellen_US
dc.subjecthuman developmenten_US
dc.subjectovaryen_US
dc.subjectsex developmenten_US
dc.subjectsteroidogenesisen_US
dc.subjecttestisen_US
dc.titleA genomic atlas of human adrenal and gonad development.en_US
dc.typeJournal Article
rioxxterms.versionofrecord10.12688/wellcomeopenres.11253.2en_US
rioxxterms.licenseref.startdate2017-04-07en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfWellcome Open Resen_US
pubs.notesNo embargoen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.)
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished onlineen_US
pubs.volume2en_US
pubs.embargo.termsNo embargoen_US
icr.researchteamTranslational Genomicsen_US
dc.contributor.icrauthorHubank, Michaelen_US
dc.contributor.icrauthorMarsden,en_US


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