Transcriptional signature in microglia associated with Aβ plaque phagocytosis

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dc.contributor.authorGrubman, A.
dc.contributor.authorChoo, X.Y.
dc.contributor.authorChew, G.
dc.contributor.authorOuyang, J.F.
dc.contributor.authorSun, G.
dc.contributor.authorCroft, N.P.
dc.contributor.authorRossello, F.J.
dc.contributor.authorSimmons, R.
dc.contributor.authorBuckberry, S.
dc.contributor.authorLandin, D.V.
dc.contributor.authorPflueger, J.
dc.contributor.authorVandekolk, T.H.
dc.contributor.authorAbay, Z.
dc.contributor.authorZhou, Y.
dc.contributor.authorLiu, X.
dc.contributor.authorChen, J.
dc.contributor.authorLarcombe, M.
dc.contributor.authorHaynes, J.M.
dc.contributor.authorMcLean, C.
dc.contributor.authorWilliams, S.
dc.contributor.authoret al.
dc.date.issued2021
dc.description.abstractThe role of microglia cells in Alzheimer’s disease (AD) is well recognized, however their molecular and functional diversity remain unclear. Here, we isolated amyloid plaque-containing (using labelling with methoxy-XO4, XO4⁺) and non-containing (XO4⁻) microglia from an AD mouse model. Transcriptomics analysis identified different transcriptional trajectories in ageing and AD mice. XO4⁺ microglial transcriptomes demonstrated dysregulated expression of genes associated with late onset AD. We further showed that the transcriptional program associated with XO4⁺ microglia from mice is present in a subset of human microglia isolated from brains of individuals with AD. XO4⁻ microglia displayed transcriptional signatures associated with accelerated ageing and contained more intracellular post-synaptic material than XO4⁺ microglia, despite reduced active synaptosome phagocytosis. We identified HIF1α as potentially regulating synaptosome phagocytosis in vitro using primary human microglia, and BV2 mouse microglial cells. Together, these findings provide insight into molecular mechanisms underpinning the functional diversity of microglia in AD.
dc.description.statementofresponsibilityAlexandra Grubman, Xin Yi Choo, Gabriel Chew, John F. Ouyang, Guizhi Sun, Nathan P. Croft, Fernando J. Rossello, Rebecca Simmons, Sam Buckberry, Dulce Vargas Landin, Jahnvi Pflueger, Teresa H. Vandekolk, Zehra Abay, Yichen Zhou, Xiaodong Liu, Joseph Chen, Michael Larcombe, John M. Haynes, Catriona McLean, Sarah Williams, Siew Yeen Chai, Trevor Wilson, Ryan Lister, Colin W. Pouton, Anthony W. Purcell, Owen J.L. Rackham, Enrico Petretto, Jose M. Polo
dc.identifier.citationNature Communications, 2021; 12(1):3015-1-3015-22
dc.identifier.doi10.1038/s41467-021-23111-1
dc.identifier.issn2041-1723
dc.identifier.issn2041-1723
dc.identifier.orcidPolo, J.M. [0000-0002-2531-778X]
dc.identifier.urihttps://hdl.handle.net/2440/133831
dc.language.isoen
dc.publisherSpringer Nature
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/GNT1097461
dc.rights© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.source.urihttps://doi.org/10.1038/s41467-021-23111-1
dc.subjectAmyloid plaque
dc.subject.meshBrain
dc.subject.meshMicroglia
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshAlzheimer Disease
dc.subject.meshDisease Models, Animal
dc.subject.meshPhagocytosis
dc.subject.meshGene Expression
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshMiddle Aged
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit
dc.subject.meshGene Regulatory Networks
dc.subject.meshPlaque, Amyloid
dc.subject.meshTranscriptome
dc.titleTranscriptional signature in microglia associated with Aβ plaque phagocytosis
dc.title.alternativeTranscriptional signature in microglia associated with Abeta plaque phagocytosis
dc.typeJournal article
pubs.publication-statusPublished

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