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Astrocyte heterogeneity has been well explored, but our understanding of white matter (WM) astrocytes and their distinctions from gray matter (GM) astrocytes remains limited. Here, we compared astrocytes from cortical GM and WM/corpus callosum (WM/CC) using single-cell RNA sequencing and spatial transcriptomics of the murine forebrain. The comparison revealed similarities but also significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks specific to WM astrocytes with molecular properties also shared with human WM astrocytes. When we compared murine astrocytes from two different WM regions, the cortex and cerebellum, we found that they exhibited distinct, region-specific molecular properties, with the cerebellum lacking, for example, a specific cluster of WM astrocytes expressing progenitor and proliferation genes. Functional experiments confirmed astrocyte proliferation in the WM/CC, but not in the cerebellar WM, suggesting that the WM/CC may be a source of continued astrogenesis.
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Created: 4th Aug 2026 at 11:34
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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/
Neuronal loss in acute or chronic brain disease could be treated by neuronal replacement strategies, such as transplantation of young neurons, if they integrate properly into the existing networks. Here we explore the cell-based and molecular mechanisms causing hyperinnervation and overshoot loss of input connectivity as well as the newly discovered hurdle in output connectivity, the lack of myelination. Candidate as well as unbiased approaches are pursued to identify the critical checkpoints and ...
Submitter: Camilla Giudici
Studies: Astrocyte heterogeneity reveals region-specific astrogenesis in the whit..., Brain injury environment critically influences the connectivity of trans..., Direct neuronal reprogramming of NDUFS4 patient cells identifies the unf..., Direct neuronal reprogramming of mouse astrocytes is associated with mul..., Heterogeneity of neurons reprogrammed from spinal cord astrocytes by the..., Injury-specific factors in the cerebrospinal fluid regulate astrocyte pl..., Single Cell Deletion of the Transcription Factors Trps1 and Sox9 in Astr...
Assays: Expression profiling, Expression profiling by array, Expression profiling: Bulk RNA-seq (human), Expression profiling: Bulk RNA-seq (mouse), Expression profiling: Single-cell multiome (scRNA-seq + scATAC-seq), Bul..., Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: Spatial Transcriptomics (mouse), Expression profiling: scRNA-seq (human) (Day 20), Expression profiling: scRNA-seq (human) (Day 5), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Expression profiling: scRNA-seq (mouse), Shotgun proteomics (human), Shotgun proteomics (mouse), scRNA-seq and scATAC-seq
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Submitter: Camilla Giudici
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: C05 - Glial checkpoints for neuronal circuitry ...
Organisms: Mouse
SOPs: No SOPs
Data files: Spatial transcriptomic of mus musculus: adult c...
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Submitter: Camilla Giudici
Assay type: Transcriptomics
Technology type: Sequencing
Investigation: C05 - Glial checkpoints for neuronal circuitry ...
Organisms: Mouse
SOPs: No SOPs
Data files: Region-specific astrocyte heterogeneity in the ..., Shiny-based web visualisation: Astrocyte hetero...
Snapshots: No snapshots
Astrocyte heterogeneity has been well explored, but our understanding of white matter (WM) astrocytes and their distinctions from grey matter (GM) astrocytes remains limited. Here, we compared astrocytes from cortical GM and WM/corpus callosum (WM/CC) using single cell RNA-sequencing (scRNA-seq) and spatial transcriptomics of the murine forebrain. The comparison revealed similarities, but also significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks ...
Creators: None
Submitter: Camilla Giudici
Investigations: C05 - Glial checkpoints for neuronal circuitry ...
Astrocyte heterogeneity has been extensively studied, but our understanding of white matter (WM) astrocytes and their distinctions from grey matter (GM) astrocytes remains limited. We directly compared astrocytes from cortical GM, WM, and the subependymal zone using scRNA-seq and spatial transcriptomics of murine forebrain sections. The comparison revealed significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks specific to WM astrocytes. Furthermore, ...
Creators: None
Submitter: Camilla Giudici
Investigations: C05 - Glial checkpoints for neuronal circuitry ...
Astrocyte heterogeneity has been extensively studied, but our understanding of white matter (WM) astrocytes and their distinctions from grey matter (GM) astrocytes remains limited. We directly compared astrocytes from cortical GM, WM, and the subependymal zone using scRNA-seq and spatial transcriptomics of murine forebrain sections. The comparison revealed significant differences between WM and GM astrocytes, including cytoskeletal and metabolic hallmarks specific to WM astrocytes. Furthermore, ...
Creators: None
Submitter: Camilla Giudici
Abstract (Expand)
Authors: Riccardo Bocchi, Manja Thorwirth, Tatiana Simon-Ebert, Christina Koupourtidou, Solène Clavreul, Keegan Kolf, Patrizia Della Vecchia, Sara Bottes, Sebastian Jessberger, Jiafeng Zhou, Gulzar Wani, Gregor-Alexander Pilz, Jovica Ninkovic, Annalisa Buffo, Swetlana Sirko, Magdalena Götz, Judith Fischer-Sternjak
Date Published: 24th Feb 2025
Publication Type: Journal Article
DOI: 10.1038/s41593-025-01878-6
Citation: Nat Neurosci 28(3):457-469.
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https://orcid.org/0000-0003-1551-9203