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

Summary: 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 tr...

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Main Authors: Huiwen Qin, Shuguang Yu, Ruyi Han, Jie He
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725002797
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author Huiwen Qin
Shuguang Yu
Ruyi Han
Jie He
author_facet Huiwen Qin
Shuguang Yu
Ruyi Han
Jie He
author_sort Huiwen Qin
collection DOAJ
description Summary: 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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spelling doaj-art-8268c53700ec4979b0d80fc09e1856fd2025-08-20T02:08:34ZengElsevierCell Reports2211-12472025-04-0144411550810.1016/j.celrep.2025.115508Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structureHuiwen Qin0Shuguang Yu1Ruyi Han2Jie He3State Key Laboratory of Neuroscience, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaState Key Laboratory of Neuroscience, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaDepartment of Ophthalmology, Eye, ENT Hospital of Fudan University, Shanghai 200031, China; Shanghai Key Laboratory of Visual Impairment, Restoration, Fudan University, Shanghai 200031, China; NHC Key Laboratory of Myopia, Fudan University, Shanghai 200031, ChinaState Key Laboratory of Neuroscience, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725002797CP: NeuroscienceCP: Cell biology
spellingShingle Huiwen Qin
Shuguang Yu
Ruyi Han
Jie He
Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure
Cell Reports
CP: Neuroscience
CP: Cell biology
title Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure
title_full Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure
title_fullStr Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure
title_full_unstemmed Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure
title_short Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure
title_sort age dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure
topic CP: Neuroscience
CP: Cell biology
url http://www.sciencedirect.com/science/article/pii/S2211124725002797
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AT shuguangyu agedependentglialheterogeneityandtraumaticinjuryresponsesinavertebratebrainstructure
AT ruyihan agedependentglialheterogeneityandtraumaticinjuryresponsesinavertebratebrainstructure
AT jiehe agedependentglialheterogeneityandtraumaticinjuryresponsesinavertebratebrainstructure