Koupourtidou, C.* ; Schwarz, V.* ; Aliee, H. ; Frerich, S.* ; Fischer-Sternjak, J. ; Bocchi, R. ; Simon-Ebert, T. ; Bai, X.* ; Sirko, S. ; Kirchhoff, F.* ; Dichgans, M.* ; Götz, M. ; Theis, F.J. ; Ninkovic, J.
Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex.
Nat. Commun. 15:2866 (2024)
Traumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combine spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured male murine cerebral cortex, and identify specific states of different glial cells contributing to this signature. Interestingly, distinct glial cells share a large fraction of injury-regulated genes, including inflammatory programs downstream of the innate immune-associated pathways Cxcr3 and Tlr1/2. Systemic manipulation of these pathways decreases the reactivity state of glial cells associated with poor regeneration. The functional relevance of the discovered shared signature of glial cells highlights the importance of our resource enabling comprehensive analysis of early events after brain injury.
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Publication type
Article: Journal article
Document type
Scientific Article
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Editors
Keywords
Astrocyte Reactivity; Brain-injury; Progenitors; Activation; Physiology; Microglia; Responses; Growth; Cxcr3
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Language
english
Publication Year
2024
Prepublished in Year
0
HGF-reported in Year
2024
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
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Volume: 15,
Issue: 1,
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Article Number: 2866
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Nature Publishing Group
Publishing Place
London
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Peer reviewed
POF-Topic(s)
30204 - Cell Programming and Repair
30205 - Bioengineering and Digital Health
Research field(s)
Stem Cell and Neuroscience
Enabling and Novel Technologies
PSP Element(s)
G-500800-001
G-503800-001
Grants
Vascular Dementia Research Foundation
ERA-NET Neuron
European Union's Horizon Europe (European Innovation Council) programme
Leducq Foundation
Ampro Helmholtz Alliance
Fritz Thyssen Stiftung
German Research Foundation (DFG)
Copyright
Erfassungsdatum
2024-05-16