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001     272577
005     20241017164443.0
024 7 _ |a 10.1186/s12974-024-03242-0
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037 _ _ |a DZNE-2024-01198
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Luczak-Sobotkowska, Zuzanna M
|b 0
245 _ _ |a Tracking changes in functionality and morphology of repopulated microglia in young and old mice.
260 _ _ |a London
|c 2024
|b BioMed Central
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520 _ _ |a Microglia (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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650 _ 7 |a Aging
|2 Other
650 _ 7 |a CSF1R inhibitors
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650 _ 7 |a Microglia repopulation
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650 _ 7 |a Microglial heterogeneity
|2 Other
650 _ 7 |a ScRNA-seq
|2 Other
650 _ 7 |a Transcriptomics
|2 Other
650 _ 7 |a Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Microglia: metabolism
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Aging: physiology
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Brain: cytology
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: metabolism
|2 MeSH
650 _ 2 |a Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: genetics
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650 _ 2 |a Single-Cell Analysis
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700 1 _ |a Rosa, Patrycja
|b 1
700 1 _ |a Lopez, Maria Banqueri
|b 2
700 1 _ |a Ochocka, Natalia
|b 3
700 1 _ |a Kiryk, Anna
|b 4
700 1 _ |a Lenkiewicz, Anna M
|b 5
700 1 _ |a Fuhrmann, Martin
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700 1 _ |a Jankowski, Aleksander
|0 0000-0002-2212-6224
|b 7
700 1 _ |a Kaminska, Bozena
|0 0000-0002-2642-4616
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773 _ _ |a 10.1186/s12974-024-03242-0
|g Vol. 21, no. 1, p. 248
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|t Journal of neuroinflammation
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|y 2024
|x 1742-2094
856 4 _ |u https://pub.dzne.de/record/272577/files/DZNE-2024-01198_Supp.pdf
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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