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dc.contributor.authorBall, Gareth
dc.contributor.authorSeidlitz, Jakob
dc.contributor.authorO’Muircheartaigh, Jonathan
dc.contributor.authorDimitrova, Ralica
dc.contributor.authorFenchel, Daphna
dc.contributor.authorMakropoulos, Antonios
dc.contributor.authorChristiaens, Daan
dc.contributor.authorSchuh, Andreas
dc.contributor.authorPasserat-Palmbach, Jonathan
dc.contributor.authorHutter, Jana
dc.contributor.authorCordero-Grande, Lucilio
dc.contributor.authorHughes, Emer
dc.contributor.authorPrice, Anthony
dc.contributor.authorHajnal, Jo V.
dc.contributor.authorRueckert, Daniel
dc.contributor.authorRobinson, Emma C.
dc.contributor.authorEdwards, A David
dc.date.accessioned2020-12-08T04:09:28Z
dc.date.available2020-12-08T04:09:28Z
dc.date.issued2020-11-23
dc.date.submitted2020-04-20
dc.identifier.issn1544-9173
dc.identifier.otherpbiology-d-20-01068
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/314881
dc.descriptionFunder: Royal Children's Hospital Foundation; funder-id: http://dx.doi.org/10.13039/100014607
dc.descriptionFunder: FP7 Ideas: European Research Council (); Grant(s): 319456
dc.description.abstractInterruption to gestation through preterm birth can significantly impact cortical development and have long-lasting adverse effects on neurodevelopmental outcome. We compared cortical morphology captured by high-resolution, multimodal magnetic resonance imaging (MRI) in n = 292 healthy newborn infants (mean age at birth = 39.9 weeks) with regional patterns of gene expression in the fetal cortex across gestation (n = 156 samples from 16 brains, aged 12 to 37 postconceptional weeks [pcw]). We tested the hypothesis that noninvasive measures of cortical structure at birth mirror areal differences in cortical gene expression across gestation, and in a cohort of n = 64 preterm infants (mean age at birth = 32.0 weeks), we tested whether cortical alterations observed after preterm birth were associated with altered gene expression in specific developmental cell populations. Neonatal cortical structure was aligned to differential patterns of cell-specific gene expression in the fetal cortex. Principal component analysis (PCA) of 6 measures of cortical morphology and microstructure showed that cortical regions were ordered along a principal axis, with primary cortex clearly separated from heteromodal cortex. This axis was correlated with estimated tissue maturity, indexed by differential expression of genes expressed by progenitor cells and neurons, and engaged in stem cell differentiation, neuron migration, and forebrain development. Preterm birth was associated with altered regional MRI metrics and patterns of differential gene expression in glial cell populations. The spatial patterning of gene expression in the developing cortex was thus mirrored by regional variation in cortical morphology and microstructure at term, and this was disrupted by preterm birth. This work provides a framework to link molecular mechanisms to noninvasive measures of cortical development in early life and highlights novel pathways to injury in neonatal populations at increased risk of neurodevelopmental disorder.
dc.languageen
dc.publisherPublic Library of Science
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch Article
dc.subjectBiology and life sciences
dc.subjectMedicine and health sciences
dc.subjectResearch and analysis methods
dc.titleCortical morphology at birth reflects spatiotemporal patterns of gene expression in the fetal human brain
dc.typeArticle
dc.date.updated2020-12-08T04:09:27Z
prism.issueIdentifier11
prism.publicationNamePLOS Biology
prism.volume18
dc.identifier.doi10.17863/CAM.61987
dcterms.dateAccepted2020-11-02
rioxxterms.versionofrecord10.1371/journal.pbio.3000976
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisoreditor: Hilgetag, Claus C.
dc.contributor.orcidBall, Gareth [0000-0003-3509-1435]
dc.contributor.orcidSeidlitz, Jakob [0000-0002-8164-7476]
dc.contributor.orcidDimitrova, Ralica [0000-0002-6903-7990]
dc.contributor.orcidChristiaens, Daan [0000-0001-8323-5451]
dc.contributor.orcidSchuh, Andreas [0000-0002-8214-116X]
dc.contributor.orcidRueckert, Daniel [0000-0002-5683-5889]
dc.contributor.orcidEdwards, A David [0000-0003-4801-7066]
dc.identifier.eissn1545-7885
pubs.funder-project-idFlemish Research Foundation (FWO/12ZV420N)


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's licence is described as Attribution 4.0 International (CC BY 4.0)