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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)

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Open Access Green as soon as Postprint is submitted to ZB.

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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, Pages: 3149–3161

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