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Competitive repopulation of an empty microglial niche yields functionally distinct subsets of microglia-like cells
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2018 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 4845Article in journal (Refereed) Published
Abstract [en]

Circulating monocytes can compete for virtually any tissue macrophage niche and become long-lived replacements that are phenotypically indistinguishable from their embryonic counterparts. As the factors regulating this process are incompletely understood, we studied niche competition in the brain by depleting microglia with >95% efficiency using Cx3cr1CreER/+R26DTA/+ mice and monitored long-term repopulation. Here we show that the microglial niche is repopulated within weeks by a combination of local proliferation of CX3CR1+F4/80lowClec12a microglia and infiltration of CX3CR1+F4/80hiClec12a+ macrophages that arise directly from Ly6Chi monocytes. This colonization is independent of blood brain barrier breakdown, paralleled by vascular activation, and regulated by type I interferon. Ly6Chi monocytes upregulate microglia gene expression and adopt microglia DNA methylation signatures, but retain a distinct gene signature from proliferating microglia, displaying altered surface marker expression, phagocytic capacity and cytokine production. Our results demonstrate that monocytes are imprinted by the CNS microenvironment but remain transcriptionally, epigenetically and functionally distinct.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018. Vol. 9, article id 4845
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Cell and Molecular Biology
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URN: urn:nbn:se:umu:diva-154942DOI: 10.1038/s41467-018-07295-7ISI: 000450405300002PubMedID: 30451869Scopus ID: 2-s2.0-85056717930OAI: oai:DiVA.org:umu-154942DiVA, id: diva2:1276086
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved

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Nilsson, EmmaÖverby, Anna K.

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CiteExportLink to record
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