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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| Format: | Article |
| Language: | English |
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Elsevier
2025-04-01
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| 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. |
| format | Article |
| id | doaj-art-8268c53700ec4979b0d80fc09e1856fd |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| 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 |
| work_keys_str_mv | AT huiwenqin agedependentglialheterogeneityandtraumaticinjuryresponsesinavertebratebrainstructure AT shuguangyu agedependentglialheterogeneityandtraumaticinjuryresponsesinavertebratebrainstructure AT ruyihan agedependentglialheterogeneityandtraumaticinjuryresponsesinavertebratebrainstructure AT jiehe agedependentglialheterogeneityandtraumaticinjuryresponsesinavertebratebrainstructure |