Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury.
Immunity
; 57(2): 349-363.e9, 2024 Feb 13.
Article
in En
| MEDLINE
| ID: mdl-38309272
ABSTRACT
Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1ï¼Spp1ï¼ to label and track DAM-like microglia during brain injury and recovery. Fate mapping of Spp1+ microglia during stroke in juvenile mice revealed an irreversible state of DAM-like microglia that were ultimately eliminated from the injured brain. By contrast, DAM-like microglia in the neonatal stroke models exhibited high plasticity, regaining a homeostatic signature and integrating into the microglial network after recovery. Furthermore, neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitized to subsequent immune challenges. Therefore, our findings highlight the plasticity and innate immune memory of neonatal microglia, shedding light on the fate of DAM-like microglia in various neuropathological conditions.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Brain Injuries
/
Stroke
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2024
Type:
Article
Affiliation country:
China