Krishnan, ML;
Van Steenwinckel, J;
Schang, A-L;
Yan, J;
Arnadottir, J;
Le Charpentier, T;
Csaba, Z;
... Gressens, P; + view all
(2017)
Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants.
Nature Communications
, 8
, Article 428. 10.1038/s41467-017-00422-w.
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Abstract
Preterm birth places infants in an adverse environment that leads to abnormal brain development and cerebral injury through a poorly understood mechanism known to involve neuroinflammation. In this study, we integrate human and mouse molecular and neuroimaging data to investigate the role of microglia in preterm white matter damage. Using a mouse model where encephalopathy of prematurity is induced by systemic interleukin-1β administration, we undertake gene network analysis of the microglial transcriptomic response to injury, extend this by analysis of protein-protein interactions, transcription factors and human brain gene expression, and translate findings to living infants using imaging genomics. We show that DLG4 (PSD95) protein is synthesised by microglia in immature mouse and human, developmentally regulated, and modulated by inflammation; DLG4 is a hub protein in the microglial inflammatory response; and genetic variation in DLG4 is associated with structural differences in the preterm infant brain. DLG4 is thus apparently involved in brain development and impacts inter-individual susceptibility to injury after preterm birth.
| Type: | Article |
|---|---|
| Title: | Integrative genomics of microglia implicates DLG4 (PSD95) in the white matter development of preterm infants |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-017-00422-w |
| Publisher version: | http://dx.doi.org/10.1038/s41467-017-00422-w |
| Language: | English |
| Additional information: | © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Experimental models of disease, Gene regulatory networks, Glial development, Paediatric research |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10057696 |
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