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Publication : Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury.

First Author  Lan Y Year  2024
Journal  Immunity Volume  57
Issue  2 Pages  349-363.e9
PubMed ID  38309272 Mgi Jnum  J:346654
Mgi Id  MGI:7614058 Doi  10.1016/j.immuni.2024.01.008
Citation  Lan Y, et al. (2024) Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury. Immunity 57(2):349-363.e9
abstractText  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 1Spp1 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.
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