Journal Article

DZNE-2024-01198

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Tracking changes in functionality and morphology of repopulated microglia in young and old mice.

Luczak-Sobotkowska, Z. M. ; Rosa, P. ; Lopez, M. B. ; Ochocka, N. ; Kiryk, A. ; Lenkiewicz, A. M. ; Fuhrmann, M.DZNE* ; Jankowski, A. ; Kaminska, B.

2024
BioMed Central London

This record in other databases:  

Please use a persistent id in citations: doi:10.1186/s12974-024-03242-0

Abstract: 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.

Keyword(s): Animals (MeSH) ; Microglia: metabolism (MeSH) ; Mice (MeSH) ; Aging: physiology (MeSH) ; Mice, Inbred C57BL (MeSH) ; Brain: cytology (MeSH) ; Brain: metabolism (MeSH) ; Male (MeSH) ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: metabolism (MeSH) ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor: genetics (MeSH) ; Single-Cell Analysis (MeSH) ; Aging ; CSF1R inhibitors ; Microglia repopulation ; Microglial heterogeneity ; ScRNA-seq ; Transcriptomics ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

---

Contributing Institute(s):

1. Neuroimmunology and Imaging (AG Fuhrmann)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---