PUBLICATION
Cell competition for neuron-derived trophic factor controls the turnover and lifespan of microglia
- Authors
- Yu, T., Kuang, H., Wu, X., Huang, Y., Wang, J., Wen, Z.
- ID
- ZDB-PUB-230617-35
- Date
- 2023
- Source
- Science advances 9: eadf9790eadf9790 (Journal)
- Registered Authors
- Wen, Zilong
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Competition
- Interleukins/metabolism
- Longevity
- Mice
- Microglia*/metabolism
- Neurons/metabolism
- Receptor Protein-Tyrosine Kinases/metabolism
- Zebrafish*/metabolism
- PubMed
- 37327343 Full text @ Sci Adv
Citation
Yu, T., Kuang, H., Wu, X., Huang, Y., Wang, J., Wen, Z. (2023) Cell competition for neuron-derived trophic factor controls the turnover and lifespan of microglia. Science advances. 9:eadf9790eadf9790.
Abstract
Microglia are brain-resident macrophages capable of long-term maintenance through self-renewal. Yet the mechanism governing the turnover and lifespan of microglia remains unknown. In zebrafish, microglia arise from two sources, rostral blood island (RBI) and aorta-gonad-mesonephros (AGM). The RBI-derived microglia are born early but have a short lifespan and diminish in adulthood, while the AGM-derived microglia emerge later and are capable of long-term maintenance in adulthood. Here, we show that the attenuation of RBI microglia is due to their less competitiveness for neuron-derived interleukin-34 (Il34) caused by age-dependent decline of colony-stimulating factor-1 receptor a (csf1ra). Alterations of Il34/Csf1ra levels and removal of AGM microglia revamp the proportion and lifespan of RBI microglia. The csf1ra/CSF1R expression in zebrafish AGM-derived microglia and murine adult microglia also undergo age-dependent decline, leading to the elimination of aged microglia. Our study reveals cell competition as a general mechanism controlling the turnover and lifespan of microglia.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping