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000272577 037__ $$aDZNE-2024-01198
000272577 041__ $$aEnglish
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000272577 1001_ $$aLuczak-Sobotkowska, Zuzanna M$$b0
000272577 245__ $$aTracking changes in functionality and morphology of repopulated microglia in young and old mice.
000272577 260__ $$aLondon$$bBioMed Central$$c2024
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000272577 520__ $$aMicroglia (MG) are myeloid cells of the central nervous system that support homeostasis and instigate neuroinflammation in pathologies. Single-cell RNA sequencing (scRNA-seq) revealed the functional heterogeneity of MG in mouse brains. Microglia are self-renewing cells and inhibition of colony-stimulating factor 1 receptor (CSF1R) signaling depletes microglia which rapidly repopulate. The functions of repopulated microglia are poorly known.We combined scRNA-seq, bulk RNA-seq, immunofluorescence, and confocal imaging to study the functionalities and morphology of repopulated microglia.A CSRF1R inhibitor (BLZ-945) depleted microglia within 21 days and a number of microglia was fully restored within 7 days, as confirmed by TMEM119 staining and flow cytometry. ScRNA-seq and computational analyses demonstrate that repopulated microglia originated from preexisting progenitors and reconstituted functional clusters but upregulated inflammatory genes. Percentages of proliferating, immature microglia displaying inflammatory gene expression increased in aging mice. Morphometric analysis of MG cell body and branching revealed a distinct morphology of repopulated MG, particularly in brains of old mice. We demonstrate that with aging some repopulated MG fail to reach the homeostatic phenotype. These differences may contribute to the deterioration of MG protective functions with age.
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000272577 650_7 $$2Other$$aAging
000272577 650_7 $$2Other$$aCSF1R inhibitors
000272577 650_7 $$2Other$$aMicroglia repopulation
000272577 650_7 $$2Other$$aMicroglial heterogeneity
000272577 650_7 $$2Other$$aScRNA-seq
000272577 650_7 $$2Other$$aTranscriptomics
000272577 650_7 $$2NLM Chemicals$$aReceptors, Granulocyte-Macrophage Colony-Stimulating Factor
000272577 650_2 $$2MeSH$$aAnimals
000272577 650_2 $$2MeSH$$aMicroglia: metabolism
000272577 650_2 $$2MeSH$$aMice
000272577 650_2 $$2MeSH$$aAging: physiology
000272577 650_2 $$2MeSH$$aMice, Inbred C57BL
000272577 650_2 $$2MeSH$$aBrain: cytology
000272577 650_2 $$2MeSH$$aBrain: metabolism
000272577 650_2 $$2MeSH$$aMale
000272577 650_2 $$2MeSH$$aReceptors, Granulocyte-Macrophage Colony-Stimulating Factor: metabolism
000272577 650_2 $$2MeSH$$aReceptors, Granulocyte-Macrophage Colony-Stimulating Factor: genetics
000272577 650_2 $$2MeSH$$aSingle-Cell Analysis
000272577 7001_ $$aRosa, Patrycja$$b1
000272577 7001_ $$aLopez, Maria Banqueri$$b2
000272577 7001_ $$aOchocka, Natalia$$b3
000272577 7001_ $$aKiryk, Anna$$b4
000272577 7001_ $$aLenkiewicz, Anna M$$b5
000272577 7001_ $$0P:(DE-2719)2679991$$aFuhrmann, Martin$$b6$$udzne
000272577 7001_ $$00000-0002-2212-6224$$aJankowski, Aleksander$$b7
000272577 7001_ $$00000-0002-2642-4616$$aKaminska, Bozena$$b8
000272577 773__ $$0PERI:(DE-600)2156455-3$$a10.1186/s12974-024-03242-0$$gVol. 21, no. 1, p. 248$$n1$$p248$$tJournal of neuroinflammation$$v21$$x1742-2094$$y2024
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