PUBLICATION

Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure

Authors
Qin, H., Yu, S., Han, R., He, J.
ID
ZDB-PUB-250409-5
Date
2025
Source
Cell Reports   44: 115508115508 (Journal)
Registered Authors
He, Jie, Qin, Huiwen, Yu, Shuguang
Keywords
CP: Cell biology, CP: Neuroscience, age dependent, glial dynamics, microglia, oligodendrocyte-lineage cells, post-embryonic developmental stage, radial astrocytes, traumatic brain injury, zebrafish optic tectum
MeSH Terms
  • Transcriptome
  • Zebrafish
  • Aging*/pathology
  • Age Factors
  • Brain*/metabolism
  • Brain*/pathology
  • Microglia/metabolism
  • Microglia/pathology
  • Animals
  • Astrocytes/metabolism
  • Brain Injuries, Traumatic*/genetics
  • Brain Injuries, Traumatic*/metabolism
  • Brain Injuries, Traumatic*/pathology
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Neuroglia*/metabolism
  • Neuroglia*/pathology
  • Chemokine CXCL12/metabolism
PubMed
40198221 Full text @ Cell Rep.
Abstract
The progression of traumatic brain injury (TBI) pathology is significantly influenced by age and involves a complex interplay of glial cells. However, the influence of age on the glial dynamics and their TBI responses remains mostly unexplored. Here, we obtain a comprehensive single-cell transcriptome atlas of three major glial types under the physiological and TBI conditions across four post-embryonic life stages in the zebrafish midbrain optic tectum. We identify a library of glial subtypes and states with specific age-dependent patterns that respond distinctly to TBI. Combining the glial interactome analysis and CRISPR-Cas9-mediated gene disruption, we reveal the essential roles of dla-notch3 and cxcl12a-cxcr4b interactions in the early-larval-stage-specific unresponsiveness of radial astrocytes to TBI and the TBI-induced age-independent recruitment of microglia to injury sites, respectively. Overall, our findings provide the molecular and cellular framework of TBI-induced age-related glial dynamics in vertebrate brains.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping