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Sirko, S. ; Schichor, C.* ; Della Vecchia, P.* ; Metzger, F.* ; Sonsalla, G. ; Simon, T.* ; Bürkle, M.* ; Kalpazidou, S.* ; Ninkovic, J. ; Masserdotti, G. ; Sauniere, J.F.* ; Iacobelli, V.* ; Iacobelli, S.* ; Delbridge, C.* ; Hauck, S.M. ; Tonn, J.C.* ; Götz, M.

Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain.

Nat. Med. 29, 3149–3161 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood-brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 3 Binding-protein; Reactive Astrocytes; Progenitor Cells; Neural Stem; Biomarkers; Lgals3bp; Lectin; Growth; Cancer; Tissue
ISSN (print) / ISBN 1078-8956
e-ISSN 1546-170X
Journal Nature medicine
Quellenangaben Volume: 29, Issue: , Pages: 3149–3161 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Stem Cell Research (ISF)
CF Metabolomics & Proteomics (CF-MPC)
Grants SyNergy (EXC2145)
SPP 2306 Ferroptosis
German Research Foundation
Advanced ERC grant
European Union's Horizon 2020 research and innovation program