Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex
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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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Created: 4th Aug 2026 at 08:30
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Projects: TRR 274: Checkpoints of Central Nervous System Recovery
Institutions: Universitätsmedizin Göttingen
Projects: CRC1002: Modulatory Units in Heart Failure, TRR 274: Checkpoints of Central Nervous System Recovery, SFB 1190: Compartmental Gates and Contact Sites in Cells
Web page: Not specified
https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...
Programme: Sonderforschungsbereiche/Collaborative Research Centers
Public web page: https://www.sfb274.de/
Traumatic brain injuries (TBIs) cause primary tissue damage and activate glial cells to build glial border, thereby delineating the injured brain parenchyma from the healthy surrounding tissue. However, this necessary primary reaction of glial cells often persists. This long-lasting glial activation results in prolonged and exacerbated neuroinflammation that prevents tissue restoration. We propose that a cross-regulatory network between innate immunity pathways and EV cargo defines an important ...
Submitter: Camilla Giudici
Studies: Innate Immune Pathways Promote Oligodendrocyte Progenitor Cell Recruitme..., Shared inflammatory glial cell signature after stab wound injury, reveal...
Assays: Expression profiling: Microarray (zebrafish), Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: scRNA-seq (mouse)
Snapshots: No snapshots
Submitter: Camilla Giudici
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: B05 - Cross-talk between innate immunity and ex...
Organisms: Mouse
SOPs: No SOPs
Data files: Shared inflammatory glial cell signature after ...
Snapshots: No snapshots
Submitter: Camilla Giudici
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: B05 - Cross-talk between innate immunity and ex...
Organisms: Mouse
SOPs: No SOPs
Data files: Shared inflammatory glial cell signature after ...
Snapshots: No snapshots
Spatial transcriptomics of the intact and injured mouse cerebral cortex at 3 days post injury (dpi).
Creators: None
Submitter: Camilla Giudici
Single cell transcriptomics of all cells of the intact and injured mouse cerebral cortex at 3 and 5 days post injury (dpi), in control condition and upon inhibition of the Tlr1/2 and Cxcr3 pathways.
Creators: None
Submitter: Camilla Giudici
Investigations: B05 - Cross-talk between innate immunity and ex...
Abstract (Expand)
Authors: Christina Koupourtidou, Veronika Schwarz, Hananeh Aliee, Simon Frerich, Judith Fischer-Sternjak, Riccardo Bocchi, Tatiana Simon-Ebert, Xianshu Bai, Swetlana Sirko, Frank Kirchhoff, Martin Dichgans, Magdalena Götz, Fabian J. Theis, Jovica Ninkovic
Date Published: 3rd Apr 2024
Publication Type: Journal Article
DOI: 10.1038/s41467-024-46625-w
Citation: Nat Commun 15(1):2866.
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https://orcid.org/0000-0003-1551-9203