TY  - JOUR
AU  - Luczak-Sobotkowska, Zuzanna M
AU  - Rosa, Patrycja
AU  - Lopez, Maria Banqueri
AU  - Ochocka, Natalia
AU  - Kiryk, Anna
AU  - Lenkiewicz, Anna M
AU  - Fuhrmann, Martin
AU  - Jankowski, Aleksander
AU  - Kaminska, Bozena
TI  - Tracking changes in functionality and morphology of repopulated microglia in young and old mice.
JO  - Journal of neuroinflammation
VL  - 21
IS  - 1
SN  - 1742-2094
CY  - London
PB  - BioMed Central
M1  - DZNE-2024-01198
SP  - 248
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Microglia: metabolism
KW  - Mice
KW  - Aging: physiology
KW  - Mice, Inbred C57BL
KW  - Brain: cytology
KW  - Brain: metabolism
KW  - Male
KW  - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: metabolism
KW  - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: genetics
KW  - Single-Cell Analysis
KW  - Aging (Other)
KW  - CSF1R inhibitors (Other)
KW  - Microglia repopulation (Other)
KW  - Microglial heterogeneity (Other)
KW  - ScRNA-seq (Other)
KW  - Transcriptomics (Other)
KW  - Receptors, Granulocyte-Macrophage Colony-Stimulating Factor (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39363245
C2  - pmc:PMC11448401
DO  - DOI:10.1186/s12974-024-03242-0
UR  - https://pub.dzne.de/record/272577
ER  -